Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 11/2011

01-11-2011 | Opinion Paper

Dual biological effects of the cytokines interleukin-10 and interferon-γ

Authors: Cailin Moira Wilke, Shuang Wei, Lin Wang, Ilona Kryczek, John Kao, Weiping Zou

Published in: Cancer Immunology, Immunotherapy | Issue 11/2011

Login to get access

Abstract

It is generally thought that each cytokine exerts either immune stimulatory (inflammatory) or immune inhibitory (antiinflammatory or regulatory) biological activities. However, multiple cytokines can enact both inhibitory and stimulatory effects on the immune system. Two of these cytokines are interleukin (IL)-10 and interferon-gamma (IFNγ). IL-10 has demonstrated antitumor immunity even though it has been known for years as an immunoregulatory protein. Generally perceived as an immune stimulatory cytokine, IFNγ can also induce inhibitory molecule expression including B7-H1 (PD-L1), indoleamine 2,3-dioxygenase (IDO), and arginase on multiple cell populations (dendritic cells, tumor cells, and vascular endothelial cells). In this review, we will summarize current knowledge of the dual roles of both of these cytokines and stress the previously underappreciated stimulatory role of IL-10 and inhibitory role of IFNγ in the context of malignancy. Our progressive understanding of the dual effects of these cytokines is important for dissecting cytokine-associated pathology and provides new avenues for developing effective immune therapy against human diseases, including cancer.
Literature
1.
go back to reference Fiorentino DF, Bond MW, Mosmann TR (1989) Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170(6):2081–2095PubMedCrossRef Fiorentino DF, Bond MW, Mosmann TR (1989) Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170(6):2081–2095PubMedCrossRef
2.
go back to reference O’Garra A, Stapleton G, Dhar V, Pearce M, Schumacher J, Rugo H, Barbis D, Stall A, Cupp J, Moore K et al (1990) Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol 2(9):821–832PubMedCrossRef O’Garra A, Stapleton G, Dhar V, Pearce M, Schumacher J, Rugo H, Barbis D, Stall A, Cupp J, Moore K et al (1990) Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol 2(9):821–832PubMedCrossRef
3.
go back to reference Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M (2005) Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol 23:749–786PubMedCrossRef Galli SJ, Kalesnikoff J, Grimbaldeston MA, Piliponsky AM, Williams CM, Tsai M (2005) Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol 23:749–786PubMedCrossRef
4.
go back to reference Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ (2007) Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol 8(10):1095–1104PubMedCrossRef Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ (2007) Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol 8(10):1095–1104PubMedCrossRef
5.
go back to reference Wei S, Kryczek I, Zou L, Daniel B, Cheng P, Mottram P, Curiel T, Lange A, Zou W (2005) Plasmacytoid dendritic cells induce CD8 + regulatory T cells in human ovarian carcinoma. Cancer Res 65(12):5020–5026PubMedCrossRef Wei S, Kryczek I, Zou L, Daniel B, Cheng P, Mottram P, Curiel T, Lange A, Zou W (2005) Plasmacytoid dendritic cells induce CD8 + regulatory T cells in human ovarian carcinoma. Cancer Res 65(12):5020–5026PubMedCrossRef
6.
go back to reference Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 190(7):995–1004PubMedCrossRef Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 190(7):995–1004PubMedCrossRef
7.
go back to reference McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ (2007) TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 8(12):1390–1397PubMedCrossRef McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, Cua DJ (2007) TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 8(12):1390–1397PubMedCrossRef
8.
go back to reference Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH (2000) Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 192(9):1213–1222PubMedCrossRef Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH (2000) Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 192(9):1213–1222PubMedCrossRef
9.
go back to reference Khoo UY, Proctor IE, Macpherson AJ (1997) CD4 + T cell down-regulation in human intestinal mucosa: evidence for intestinal tolerance to luminal bacterial antigens. J Immunol 158(8):3626–3634PubMed Khoo UY, Proctor IE, Macpherson AJ (1997) CD4 + T cell down-regulation in human intestinal mucosa: evidence for intestinal tolerance to luminal bacterial antigens. J Immunol 158(8):3626–3634PubMed
10.
go back to reference Couper KN, Blount DG, Riley EM (2008) IL-10: the master regulator of immunity to infection. J Immunol 180(9):5771–5777PubMed Couper KN, Blount DG, Riley EM (2008) IL-10: the master regulator of immunity to infection. J Immunol 180(9):5771–5777PubMed
11.
go back to reference Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765PubMedCrossRef Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765PubMedCrossRef
12.
go back to reference Mosser DM, Zhang X (2008) Interleukin-10: new perspectives on an old cytokine. Immunol Rev 226:205–218PubMedCrossRef Mosser DM, Zhang X (2008) Interleukin-10: new perspectives on an old cytokine. Immunol Rev 226:205–218PubMedCrossRef
13.
go back to reference de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JE (1991) Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174(4):915–924PubMedCrossRef de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JE (1991) Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174(4):915–924PubMedCrossRef
14.
go back to reference Ding L, Linsley PS, Huang LY, Germain RN, Shevach EM (1993) IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J Immunol 151(3):1224–1234PubMed Ding L, Linsley PS, Huang LY, Germain RN, Shevach EM (1993) IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J Immunol 151(3):1224–1234PubMed
15.
go back to reference Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminki A, Alvarez RD, Emilie D, Curiel DT, Chen L, Zou W (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9(5):562–567PubMedCrossRef Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminki A, Alvarez RD, Emilie D, Curiel DT, Chen L, Zou W (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9(5):562–567PubMedCrossRef
16.
go back to reference Schandene L, Alonso-Vega C, Willems F, Gerard C, Delvaux A, Velu T, Devos R, de Boer M, Goldman M (1994) B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10. J Immunol 152(9):4368–4374PubMed Schandene L, Alonso-Vega C, Willems F, Gerard C, Delvaux A, Velu T, Devos R, de Boer M, Goldman M (1994) B7/CD28-dependent IL-5 production by human resting T cells is inhibited by IL-10. J Immunol 152(9):4368–4374PubMed
17.
go back to reference Joss A, Akdis M, Faith A, Blaser K, Akdis CA (2000) IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol 30(6):1683–1690PubMedCrossRef Joss A, Akdis M, Faith A, Blaser K, Akdis CA (2000) IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol 30(6):1683–1690PubMedCrossRef
18.
go back to reference Demangel C, Bertolino P, Britton WJ (2002) Autocrine IL-10 impairs dendritic cell (DC)-derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production. Eur J Immunol 32(4):994–1002PubMedCrossRef Demangel C, Bertolino P, Britton WJ (2002) Autocrine IL-10 impairs dendritic cell (DC)-derived immune responses to mycobacterial infection by suppressing DC trafficking to draining lymph nodes and local IL-12 production. Eur J Immunol 32(4):994–1002PubMedCrossRef
19.
20.
go back to reference Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, Kronenberg M (2009) Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 10(11):1178–1184PubMedCrossRef Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, Kronenberg M (2009) Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 10(11):1178–1184PubMedCrossRef
21.
go back to reference Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263–274PubMedCrossRef Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263–274PubMedCrossRef
22.
go back to reference Davidson NJ, Leach MW, Fort MM, Thompson-Snipes L, Kuhn R, Muller W, Berg DJ, Rennick DM (1996) T helper cell 1-type CD4 + T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. J Exp Med 184(1):241–251PubMedCrossRef Davidson NJ, Leach MW, Fort MM, Thompson-Snipes L, Kuhn R, Muller W, Berg DJ, Rennick DM (1996) T helper cell 1-type CD4 + T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. J Exp Med 184(1):241–251PubMedCrossRef
23.
go back to reference Zhou P, Streutker C, Borojevic R, Wang Y, Croitoru K (2004) IL-10 modulates intestinal damage and epithelial cell apoptosis in T cell-mediated enteropathy. Am J Physiol Gastrointest Liver Physiol 287(3):G599–G604PubMedCrossRef Zhou P, Streutker C, Borojevic R, Wang Y, Croitoru K (2004) IL-10 modulates intestinal damage and epithelial cell apoptosis in T cell-mediated enteropathy. Am J Physiol Gastrointest Liver Physiol 287(3):G599–G604PubMedCrossRef
24.
go back to reference Jarry A, Bossard C, Bou-Hanna C, Masson D, Espaze E, Denis MG, Laboisse CL (2008) Mucosal IL-10 and TGF-beta play crucial roles in preventing LPS-driven, IFN-gamma-mediated epithelial damage in human colon explants. J Clin Invest 118(3):1132–1142PubMed Jarry A, Bossard C, Bou-Hanna C, Masson D, Espaze E, Denis MG, Laboisse CL (2008) Mucosal IL-10 and TGF-beta play crucial roles in preventing LPS-driven, IFN-gamma-mediated epithelial damage in human colon explants. J Clin Invest 118(3):1132–1142PubMed
25.
go back to reference Hagenbaugh A, Sharma S, Dubinett SM, Wei SH, Aranda R, Cheroutre H, Fowell DJ, Binder S, Tsao B, Locksley RM, Moore KW, Kronenberg M (1997) Altered immune responses in interleukin 10 transgenic mice. J Exp Med 185(12):2101–2110PubMedCrossRef Hagenbaugh A, Sharma S, Dubinett SM, Wei SH, Aranda R, Cheroutre H, Fowell DJ, Binder S, Tsao B, Locksley RM, Moore KW, Kronenberg M (1997) Altered immune responses in interleukin 10 transgenic mice. J Exp Med 185(12):2101–2110PubMedCrossRef
26.
go back to reference Peters N, Sacks D (2006) Immune privilege in sites of chronic infection: Leishmania and regulatory T cells. Immunol Rev 213:159–179PubMedCrossRef Peters N, Sacks D (2006) Immune privilege in sites of chronic infection: Leishmania and regulatory T cells. Immunol Rev 213:159–179PubMedCrossRef
27.
go back to reference van der Sluijs KF, van Elden LJ, Nijhuis M, Schuurman R, Pater JM, Florquin S, Goldman M, Jansen HM, Lutter R, van der Poll T (2004) IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. J Immunol 172(12):7603–7609PubMed van der Sluijs KF, van Elden LJ, Nijhuis M, Schuurman R, Pater JM, Florquin S, Goldman M, Jansen HM, Lutter R, van der Poll T (2004) IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. J Immunol 172(12):7603–7609PubMed
28.
go back to reference Jimenez Mdel P, Walls L, Fierer J (2006) High levels of interleukin-10 impair resistance to pulmonary coccidioidomycosis in mice in part through control of nitric oxide synthase 2 expression. Infect Immun 74(6):3387–3395PubMedCrossRef Jimenez Mdel P, Walls L, Fierer J (2006) High levels of interleukin-10 impair resistance to pulmonary coccidioidomycosis in mice in part through control of nitric oxide synthase 2 expression. Infect Immun 74(6):3387–3395PubMedCrossRef
29.
go back to reference Fierer J, Walls L, Eckmann L, Yamamoto T, Kirkland TN (1998) Importance of interleukin-10 in genetic susceptibility of mice to Coccidioides immitis. Infect Immun 66(9):4397–4402PubMed Fierer J, Walls L, Eckmann L, Yamamoto T, Kirkland TN (1998) Importance of interleukin-10 in genetic susceptibility of mice to Coccidioides immitis. Infect Immun 66(9):4397–4402PubMed
30.
go back to reference Kelly JP, Bancroft GJ (1996) Administration of interleukin-10 abolishes innate resistance to Listeria monocytogenes. Eur J Immunol 26(2):356–364PubMedCrossRef Kelly JP, Bancroft GJ (1996) Administration of interleukin-10 abolishes innate resistance to Listeria monocytogenes. Eur J Immunol 26(2):356–364PubMedCrossRef
31.
go back to reference Kim BG, Joo HG, Chung IS, Chung HY, Woo HJ, Yun YS (2000) Inhibition of interleukin-10 (IL-10) production from MOPC 315 tumor cells by IL-10 antisense oligodeoxynucleotides enhances cell-mediated immune responses. Cancer Immunol Immunother 49(8):433–440PubMedCrossRef Kim BG, Joo HG, Chung IS, Chung HY, Woo HJ, Yun YS (2000) Inhibition of interleukin-10 (IL-10) production from MOPC 315 tumor cells by IL-10 antisense oligodeoxynucleotides enhances cell-mediated immune responses. Cancer Immunol Immunother 49(8):433–440PubMedCrossRef
32.
go back to reference Matar P, Rozados VR, Gervasoni SI, Scharovsky OG (2001) Down regulation of T-cell-derived IL-10 production by low-dose cyclophosphamide treatment in tumor-bearing rats restores in vitro normal lymphoproliferative response. Int Immunopharmacol 1(2):307–319PubMedCrossRef Matar P, Rozados VR, Gervasoni SI, Scharovsky OG (2001) Down regulation of T-cell-derived IL-10 production by low-dose cyclophosphamide treatment in tumor-bearing rats restores in vitro normal lymphoproliferative response. Int Immunopharmacol 1(2):307–319PubMedCrossRef
33.
go back to reference Vicari AP, Chiodoni C, Vaure C, Ait-Yahia S, Dercamp C, Matsos F, Reynard O, Taverne C, Merle P, Colombo MP, O’Garra A, Trinchieri G, Caux C (2002) Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody. J Exp Med 196(4):541–549PubMedCrossRef Vicari AP, Chiodoni C, Vaure C, Ait-Yahia S, Dercamp C, Matsos F, Reynard O, Taverne C, Merle P, Colombo MP, O’Garra A, Trinchieri G, Caux C (2002) Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody. J Exp Med 196(4):541–549PubMedCrossRef
34.
go back to reference Enk AH, Jonuleit H, Saloga J, Knop J (1997) Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int J Cancer 73(3):309–316PubMedCrossRef Enk AH, Jonuleit H, Saloga J, Knop J (1997) Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int J Cancer 73(3):309–316PubMedCrossRef
35.
go back to reference Loercher AE, Nash MA, Kavanagh JJ, Platsoucas CD, Freedman RS (1999) Identification of an IL-10-producing HLA-DR-negative monocyte subset in the malignant ascites of patients with ovarian carcinoma that inhibits cytokine protein expression and proliferation of autologous T cells. J Immunol 163(11):6251–6260PubMed Loercher AE, Nash MA, Kavanagh JJ, Platsoucas CD, Freedman RS (1999) Identification of an IL-10-producing HLA-DR-negative monocyte subset in the malignant ascites of patients with ovarian carcinoma that inhibits cytokine protein expression and proliferation of autologous T cells. J Immunol 163(11):6251–6260PubMed
36.
go back to reference De Santo C, Arscott R, Booth S, Karydis I, Jones M, Asher R, Salio M, Middleton M, Cerundolo V (2010) Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nat Immunol 11(11):1039–1046PubMedCrossRef De Santo C, Arscott R, Booth S, Karydis I, Jones M, Asher R, Salio M, Middleton M, Cerundolo V (2010) Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nat Immunol 11(11):1039–1046PubMedCrossRef
37.
go back to reference Seo N, Hayakawa S, Tokura Y (2002) Mechanisms of immune privilege for tumor cells by regulatory cytokines produced by innate and acquired immune cells. Semin Cancer Biol 12(4):291–300PubMedCrossRef Seo N, Hayakawa S, Tokura Y (2002) Mechanisms of immune privilege for tumor cells by regulatory cytokines produced by innate and acquired immune cells. Semin Cancer Biol 12(4):291–300PubMedCrossRef
38.
go back to reference Kurte M, Lopez M, Aguirre A, Escobar A, Aguillon JC, Charo J, Larsen CG, Kiessling R, Salazar-Onfray F (2004) A synthetic peptide homologous to functional domain of human IL-10 down-regulates expression of MHC class I and transporter associated with antigen processing 1/2 in human melanoma cells. J Immunol 173(3):1731–1737PubMed Kurte M, Lopez M, Aguirre A, Escobar A, Aguillon JC, Charo J, Larsen CG, Kiessling R, Salazar-Onfray F (2004) A synthetic peptide homologous to functional domain of human IL-10 down-regulates expression of MHC class I and transporter associated with antigen processing 1/2 in human melanoma cells. J Immunol 173(3):1731–1737PubMed
39.
go back to reference Kim J, Modlin RL, Moy RL, Dubinett SM, McHugh T, Nickoloff BJ, Uyemura K (1995) IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T cell immune response. J Immunol 155(4):2240–2247PubMed Kim J, Modlin RL, Moy RL, Dubinett SM, McHugh T, Nickoloff BJ, Uyemura K (1995) IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T cell immune response. J Immunol 155(4):2240–2247PubMed
40.
go back to reference Steinbrink K, Jonuleit H, Muller G, Schuler G, Knop J, Enk AH (1999) Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood 93(5):1634–1642PubMed Steinbrink K, Jonuleit H, Muller G, Schuler G, Knop J, Enk AH (1999) Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood 93(5):1634–1642PubMed
41.
go back to reference Urosevic M, Dummer R (2003) HLA-G and IL-10 expression in human cancer–different stories with the same message. Semin Cancer Biol 13(5):337–342PubMedCrossRef Urosevic M, Dummer R (2003) HLA-G and IL-10 expression in human cancer–different stories with the same message. Semin Cancer Biol 13(5):337–342PubMedCrossRef
42.
go back to reference Jovasevic VM, Gorelik L, Bluestone JA, Mokyr MB (2004) Importance of IL-10 for CTLA-4-mediated inhibition of tumor-eradicating immunity. J Immunol 172(3):1449–1454PubMed Jovasevic VM, Gorelik L, Bluestone JA, Mokyr MB (2004) Importance of IL-10 for CTLA-4-mediated inhibition of tumor-eradicating immunity. J Immunol 172(3):1449–1454PubMed
43.
go back to reference Huang M, Stolina M, Sharma S, Mao JT, Zhu L, Miller PW, Wollman J, Herschman H, Dubinett SM (1998) Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res 58(6):1208–1216PubMed Huang M, Stolina M, Sharma S, Mao JT, Zhu L, Miller PW, Wollman J, Herschman H, Dubinett SM (1998) Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res 58(6):1208–1216PubMed
44.
go back to reference Stolina M, Sharma S, Lin Y, Dohadwala M, Gardner B, Luo J, Zhu L, Kronenberg M, Miller PW, Portanova J, Lee JC, Dubinett SM (2000) Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J Immunol 164(1):361–370PubMed Stolina M, Sharma S, Lin Y, Dohadwala M, Gardner B, Luo J, Zhu L, Kronenberg M, Miller PW, Portanova J, Lee JC, Dubinett SM (2000) Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J Immunol 164(1):361–370PubMed
45.
go back to reference Sharma S, Stolina M, Yang SC, Baratelli F, Lin JF, Atianzar K, Luo J, Zhu L, Lin Y, Huang M, Dohadwala M, Batra RK, Dubinett SM (2003) Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin Cancer Res 9(3):961–968PubMed Sharma S, Stolina M, Yang SC, Baratelli F, Lin JF, Atianzar K, Luo J, Zhu L, Lin Y, Huang M, Dohadwala M, Batra RK, Dubinett SM (2003) Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin Cancer Res 9(3):961–968PubMed
46.
go back to reference Go NF, Castle BE, Barrett R, Kastelein R, Dang W, Mosmann TR, Moore KW, Howard M (1990) Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med 172(6):1625–1631PubMedCrossRef Go NF, Castle BE, Barrett R, Kastelein R, Dang W, Mosmann TR, Moore KW, Howard M (1990) Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med 172(6):1625–1631PubMedCrossRef
47.
go back to reference Rousset F, Garcia E, Defrance T, Peronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereau J (1992) Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 89(5):1890–1893PubMedCrossRef Rousset F, Garcia E, Defrance T, Peronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereau J (1992) Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 89(5):1890–1893PubMedCrossRef
48.
go back to reference Llorente L, Zou W, Levy Y, Richaud-Patin Y, Wijdenes J, Alcocer-Varela J, Morel-Fourrier B, Brouet JC, Alarcon-Segovia D, Galanaud P, Emilie D (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181(3):839–844PubMedCrossRef Llorente L, Zou W, Levy Y, Richaud-Patin Y, Wijdenes J, Alcocer-Varela J, Morel-Fourrier B, Brouet JC, Alarcon-Segovia D, Galanaud P, Emilie D (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181(3):839–844PubMedCrossRef
49.
go back to reference Levy Y, Brouet JC (1994) Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Invest 93(1):424–428PubMedCrossRef Levy Y, Brouet JC (1994) Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Invest 93(1):424–428PubMedCrossRef
50.
go back to reference Liu YJ, Mason DY, Johnson GD, Abbot S, Gregory CD, Hardie DL, Gordon J, MacLennan IC (1991) Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol 21(8):1905–1910PubMedCrossRef Liu YJ, Mason DY, Johnson GD, Abbot S, Gregory CD, Hardie DL, Gordon J, MacLennan IC (1991) Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur J Immunol 21(8):1905–1910PubMedCrossRef
51.
go back to reference MacNeil IA, Suda T, Moore KW, Mosmann TR, Zlotnik A (1990) IL-10, a novel growth cofactor for mature and immature T cells. J Immunol 145(12):4167–4173PubMed MacNeil IA, Suda T, Moore KW, Mosmann TR, Zlotnik A (1990) IL-10, a novel growth cofactor for mature and immature T cells. J Immunol 145(12):4167–4173PubMed
52.
go back to reference Chen WF, Zlotnik A (1991) IL-10: a novel cytotoxic T cell differentiation factor. J Immunol 147(2):528–534PubMed Chen WF, Zlotnik A (1991) IL-10: a novel cytotoxic T cell differentiation factor. J Immunol 147(2):528–534PubMed
53.
go back to reference Mocellin S, Marincola FM, Young HA (2005) Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 78(5):1043–1051PubMedCrossRef Mocellin S, Marincola FM, Young HA (2005) Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 78(5):1043–1051PubMedCrossRef
54.
go back to reference Suzuki T, Tahara H, Narula S, Moore KW, Robbins PD, Lotze MT (1995) Viral interleukin 10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors. J Exp Med 182(2):477–486PubMedCrossRef Suzuki T, Tahara H, Narula S, Moore KW, Robbins PD, Lotze MT (1995) Viral interleukin 10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors. J Exp Med 182(2):477–486PubMedCrossRef
55.
go back to reference Zheng LM, Ojcius DM, Garaud F, Roth C, Maxwell E, Li Z, Rong H, Chen J, Wang XY, Catino JJ, King I (1996) Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism. J Exp Med 184(2):579–584PubMedCrossRef Zheng LM, Ojcius DM, Garaud F, Roth C, Maxwell E, Li Z, Rong H, Chen J, Wang XY, Catino JJ, King I (1996) Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism. J Exp Med 184(2):579–584PubMedCrossRef
56.
go back to reference Kundu N, Fulton AM (1997) Interleukin-10 inhibits tumor metastasis, downregulates MHC class I, and enhances NK lysis. Cell Immunol 180(1):55–61PubMedCrossRef Kundu N, Fulton AM (1997) Interleukin-10 inhibits tumor metastasis, downregulates MHC class I, and enhances NK lysis. Cell Immunol 180(1):55–61PubMedCrossRef
57.
go back to reference Karre K (1993) Natural killer cells and the MHC class I pathway of peptide presentation. Semin Immunol 5(2):127–145PubMedCrossRef Karre K (1993) Natural killer cells and the MHC class I pathway of peptide presentation. Semin Immunol 5(2):127–145PubMedCrossRef
58.
go back to reference Fujii S, Shimizu K, Shimizu T, Lotze MT (2001) Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. Blood 98(7):2143–2151PubMedCrossRef Fujii S, Shimizu K, Shimizu T, Lotze MT (2001) Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. Blood 98(7):2143–2151PubMedCrossRef
59.
go back to reference Tanikawa T, Wilke CM, Kryczek I, Chen GY, Kao JY, Zou W (2011) Ablation of interleukin (IL)-10 promotes tumor development, growth and metastasis (in press) Tanikawa T, Wilke CM, Kryczek I, Chen GY, Kao JY, Zou W (2011) Ablation of interleukin (IL)-10 promotes tumor development, growth and metastasis (in press)
60.
go back to reference Zhou Z, Peng X, Insolera R, Fink DJ, Mata M (2009) Interleukin-10 provides direct trophic support to neurons. J Neurochem 110(5):1617–1627PubMedCrossRef Zhou Z, Peng X, Insolera R, Fink DJ, Mata M (2009) Interleukin-10 provides direct trophic support to neurons. J Neurochem 110(5):1617–1627PubMedCrossRef
61.
go back to reference Park HJ, Lee SJ, Kim SH, Han J, Bae J, Kim SJ, Park CG, Chun T (2011) IL-10 inhibits the starvation induced autophagy in macrophages via class I phosphatidylinositol 3-kinase (PI3 K) pathway. Mol Immunol 48(4):720–727PubMedCrossRef Park HJ, Lee SJ, Kim SH, Han J, Bae J, Kim SJ, Park CG, Chun T (2011) IL-10 inhibits the starvation induced autophagy in macrophages via class I phosphatidylinositol 3-kinase (PI3 K) pathway. Mol Immunol 48(4):720–727PubMedCrossRef
62.
go back to reference Dace DS, Khan AA, Kelly J, Apte RS (2008) Interleukin-10 promotes pathological angiogenesis by regulating macrophage response to hypoxia during development. PLoS One 3(10):e3381PubMedCrossRef Dace DS, Khan AA, Kelly J, Apte RS (2008) Interleukin-10 promotes pathological angiogenesis by regulating macrophage response to hypoxia during development. PLoS One 3(10):e3381PubMedCrossRef
63.
go back to reference Isaacs A, Lindenmann J (1957) Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 147(927):258–267PubMedCrossRef Isaacs A, Lindenmann J (1957) Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 147(927):258–267PubMedCrossRef
64.
go back to reference Isaacs A, Lindenmann J, Valentine RC (1957) Virus interference. II. Some properties of interferon. Proc R Soc Lond B Biol Sci 147(927):268–273PubMedCrossRef Isaacs A, Lindenmann J, Valentine RC (1957) Virus interference. II. Some properties of interferon. Proc R Soc Lond B Biol Sci 147(927):268–273PubMedCrossRef
65.
go back to reference Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K (1998) IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol 161(7):3400–3407PubMed Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K (1998) IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol 161(7):3400–3407PubMed
66.
go back to reference Munder M, Mallo M, Eichmann K, Modolell M (1998) Murine macrophages secrete interferon gamma upon combined stimulation with interleukin (IL)-12 and IL-18: a novel pathway of autocrine macrophage activation. J Exp Med 187(12):2103–2108PubMedCrossRef Munder M, Mallo M, Eichmann K, Modolell M (1998) Murine macrophages secrete interferon gamma upon combined stimulation with interleukin (IL)-12 and IL-18: a novel pathway of autocrine macrophage activation. J Exp Med 187(12):2103–2108PubMedCrossRef
67.
go back to reference Tominaga K, Yoshimoto T, Torigoe K, Kurimoto M, Matsui K, Hada T, Okamura H, Nakanishi K (2000) IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells. Int Immunol 12(2):151–160PubMedCrossRef Tominaga K, Yoshimoto T, Torigoe K, Kurimoto M, Matsui K, Hada T, Okamura H, Nakanishi K (2000) IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells. Int Immunol 12(2):151–160PubMedCrossRef
68.
go back to reference Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K et al (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378(6552):88–91PubMedCrossRef Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K et al (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378(6552):88–91PubMedCrossRef
69.
go back to reference Robinson D, Shibuya K, Mui A, Zonin F, Murphy E, Sana T, Hartley SB, Menon S, Kastelein R, Bazan F, O’Garra A (1997) IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB. Immunity 7(4):571–581PubMedCrossRef Robinson D, Shibuya K, Mui A, Zonin F, Murphy E, Sana T, Hartley SB, Menon S, Kastelein R, Bazan F, O’Garra A (1997) IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB. Immunity 7(4):571–581PubMedCrossRef
70.
go back to reference Yoshimoto T, Okamura H, Tagawa YI, Iwakura Y, Nakanishi K (1997) Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Proc Natl Acad Sci USA 94(8):3948–3953PubMedCrossRef Yoshimoto T, Okamura H, Tagawa YI, Iwakura Y, Nakanishi K (1997) Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Proc Natl Acad Sci USA 94(8):3948–3953PubMedCrossRef
71.
go back to reference Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6(11):836–848PubMedCrossRef Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6(11):836–848PubMedCrossRef
72.
go back to reference Blankenstein T, Qin Z (2003) Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance. Adv Cancer Res 90:179–207PubMedCrossRef Blankenstein T, Qin Z (2003) Chemical carcinogens as foreign bodies and some pitfalls regarding cancer immune surveillance. Adv Cancer Res 90:179–207PubMedCrossRef
73.
go back to reference Wallach D, Fellous M, Revel M (1982) Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature 299(5886):833–836PubMedCrossRef Wallach D, Fellous M, Revel M (1982) Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature 299(5886):833–836PubMedCrossRef
74.
go back to reference Johnson DR, Pober JS (1990) Tumor necrosis factor and immune interferon synergistically increase transcription of HLA class I heavy- and light-chain genes in vascular endothelium. Proc Natl Acad Sci USA 87(13):5183–5187PubMedCrossRef Johnson DR, Pober JS (1990) Tumor necrosis factor and immune interferon synergistically increase transcription of HLA class I heavy- and light-chain genes in vascular endothelium. Proc Natl Acad Sci USA 87(13):5183–5187PubMedCrossRef
75.
go back to reference Billiau A, Heremans H, Vandekerckhove F, Dijkmans R, Sobis H, Meulepas E, Carton H (1988) Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma. J Immunol 140(5):1506–1510PubMed Billiau A, Heremans H, Vandekerckhove F, Dijkmans R, Sobis H, Meulepas E, Carton H (1988) Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma. J Immunol 140(5):1506–1510PubMed
76.
go back to reference Mach B, Steimle V, Martinez-Soria E, Reith W (1996) Regulation of MHC class II genes: lessons from a disease. Annu Rev Immunol 14:301–331PubMedCrossRef Mach B, Steimle V, Martinez-Soria E, Reith W (1996) Regulation of MHC class II genes: lessons from a disease. Annu Rev Immunol 14:301–331PubMedCrossRef
77.
go back to reference Groettrup M, Khan S, Schwarz K, Schmidtke G (2001) Interferon-gamma inducible exchanges of 20S proteasome active site subunits: why? Biochimie 83(3–4):367–372PubMedCrossRef Groettrup M, Khan S, Schwarz K, Schmidtke G (2001) Interferon-gamma inducible exchanges of 20S proteasome active site subunits: why? Biochimie 83(3–4):367–372PubMedCrossRef
78.
go back to reference Nathan CF, Murray HW, Wiebe ME, Rubin BY (1983) Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158(3):670–689PubMedCrossRef Nathan CF, Murray HW, Wiebe ME, Rubin BY (1983) Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158(3):670–689PubMedCrossRef
79.
go back to reference Flaishon L, Hershkoviz R, Lantner F, Lider O, Alon R, Levo Y, Flavell RA, Shachar I (2000) Autocrine secretion of interferon gamma negatively regulates homing of immature B cells. J Exp Med 192(9):1381–1388PubMedCrossRef Flaishon L, Hershkoviz R, Lantner F, Lider O, Alon R, Levo Y, Flavell RA, Shachar I (2000) Autocrine secretion of interferon gamma negatively regulates homing of immature B cells. J Exp Med 192(9):1381–1388PubMedCrossRef
80.
go back to reference Finkelman FD, Katona IM, Mosmann TR, Coffman RL (1988) IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol 140(4):1022–1027PubMed Finkelman FD, Katona IM, Mosmann TR, Coffman RL (1988) IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol 140(4):1022–1027PubMed
81.
go back to reference Balkwill F, Taylor-Papadimitriou J (1978) Interferon affects both G1 and S + G2 in cells stimulated from quiescence to growth. Nature 274(5673):798–800PubMedCrossRef Balkwill F, Taylor-Papadimitriou J (1978) Interferon affects both G1 and S + G2 in cells stimulated from quiescence to growth. Nature 274(5673):798–800PubMedCrossRef
82.
go back to reference Xaus J, Cardo M, Valledor AF, Soler C, Lloberas J, Celada A (1999) Interferon gamma induces the expression of p21waf-1 and arrests macrophage cell cycle, preventing induction of apoptosis. Immunity 11(1):103–113PubMedCrossRef Xaus J, Cardo M, Valledor AF, Soler C, Lloberas J, Celada A (1999) Interferon gamma induces the expression of p21waf-1 and arrests macrophage cell cycle, preventing induction of apoptosis. Immunity 11(1):103–113PubMedCrossRef
83.
go back to reference Shiohara M, Koike K, Nakahata T (1993) Synergism of interferon-gamma and stem cell factor on the development of murine hematopoietic progenitors in serum-free culture. Blood 81(6):1435–1441PubMed Shiohara M, Koike K, Nakahata T (1993) Synergism of interferon-gamma and stem cell factor on the development of murine hematopoietic progenitors in serum-free culture. Blood 81(6):1435–1441PubMed
84.
go back to reference Gajewski TF, Fitch FW (1988) Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol 140(12):4245–4252PubMed Gajewski TF, Fitch FW (1988) Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol 140(12):4245–4252PubMed
85.
go back to reference Yoshida A, Koide Y, Uchijima M, Yoshida TO (1994) IFN-gamma induces IL-12 mRNA expression by a murine macrophage cell line, J774. Biochem Biophys Res Commun 198(3):857–861PubMedCrossRef Yoshida A, Koide Y, Uchijima M, Yoshida TO (1994) IFN-gamma induces IL-12 mRNA expression by a murine macrophage cell line, J774. Biochem Biophys Res Commun 198(3):857–861PubMedCrossRef
86.
go back to reference Kryczek I, Wei S, Gong W, Shu X, Szeliga W, Vatan L, Chen L, Wang G, Zou W (2008) Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development. J Immunol 181(9):5842–5846PubMed Kryczek I, Wei S, Gong W, Shu X, Szeliga W, Vatan L, Chen L, Wang G, Zou W (2008) Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development. J Immunol 181(9):5842–5846PubMed
87.
go back to reference Zou W, Restifo NP (2010) T(H)17 cells in tumour immunity and immunotherapy. Nat Rev Immunol 10(4):248–256PubMedCrossRef Zou W, Restifo NP (2010) T(H)17 cells in tumour immunity and immunotherapy. Nat Rev Immunol 10(4):248–256PubMedCrossRef
88.
go back to reference Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Aphale A, Vatan L, Szeliga W, Wang Y, Liu Y, Welling TH, Elder JT, Zou W (2008) Induction of IL-17 + T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181(7):4733–4741PubMed Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Aphale A, Vatan L, Szeliga W, Wang Y, Liu Y, Welling TH, Elder JT, Zou W (2008) Induction of IL-17 + T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181(7):4733–4741PubMed
89.
go back to reference Feng T, Qin H, Wang L, Benveniste EN, Elson CO, Cong Y (2011) Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J Immunol Feng T, Qin H, Wang L, Benveniste EN, Elson CO, Cong Y (2011) Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J Immunol
90.
go back to reference Huang S, Hendriks W, Althage A, Hemmi S, Bluethmann H, Kamijo R, Vilcek J, Zinkernagel RM, Aguet M (1993) Immune response in mice that lack the interferon-gamma receptor. Science 259(5102):1742–1745PubMedCrossRef Huang S, Hendriks W, Althage A, Hemmi S, Bluethmann H, Kamijo R, Vilcek J, Zinkernagel RM, Aguet M (1993) Immune response in mice that lack the interferon-gamma receptor. Science 259(5102):1742–1745PubMedCrossRef
91.
go back to reference Cantin E, Tanamachi B, Openshaw H (1999) Role for gamma interferon in control of herpes simplex virus type 1 reactivation. J Virol 73(4):3418–3423PubMed Cantin E, Tanamachi B, Openshaw H (1999) Role for gamma interferon in control of herpes simplex virus type 1 reactivation. J Virol 73(4):3418–3423PubMed
92.
go back to reference Muller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, Zinkernagel RM, Aguet M (1994) Functional role of type I and type II interferons in antiviral defense. Science 264(5167):1918–1921PubMedCrossRef Muller U, Steinhoff U, Reis LF, Hemmi S, Pavlovic J, Zinkernagel RM, Aguet M (1994) Functional role of type I and type II interferons in antiviral defense. Science 264(5167):1918–1921PubMedCrossRef
93.
go back to reference Levin M, Newport MJ, D’Souza S, Kalabalikis P, Brown IN, Lenicker HM, Agius PV, Davies EG, Thrasher A, Klein N et al (1995) Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene? Lancet 345(8942):79–83PubMedCrossRef Levin M, Newport MJ, D’Souza S, Kalabalikis P, Brown IN, Lenicker HM, Agius PV, Davies EG, Thrasher A, Klein N et al (1995) Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene? Lancet 345(8942):79–83PubMedCrossRef
94.
go back to reference Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, Levin M (1996) A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 335(26):1941–1949PubMedCrossRef Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R, Levin M (1996) A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 335(26):1941–1949PubMedCrossRef
95.
go back to reference Jouanguy E, Lamhamedi-Cherradi S, Lammas D, Dorman SE, Fondaneche MC, Dupuis S, Doffinger R, Altare F, Girdlestone J, Emile JF, Ducoulombier H, Edgar D, Clarke J, Oxelius VA, Brai M, Novelli V, Heyne K, Fischer A, Holland SM, Kumararatne DS, Schreiber RD, Casanova JL (1999) A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet 21(4):370–378PubMedCrossRef Jouanguy E, Lamhamedi-Cherradi S, Lammas D, Dorman SE, Fondaneche MC, Dupuis S, Doffinger R, Altare F, Girdlestone J, Emile JF, Ducoulombier H, Edgar D, Clarke J, Oxelius VA, Brai M, Novelli V, Heyne K, Fischer A, Holland SM, Kumararatne DS, Schreiber RD, Casanova JL (1999) A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet 21(4):370–378PubMedCrossRef
96.
go back to reference Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA (2010) Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature 465(7299):793–797PubMedCrossRef Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA (2010) Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature 465(7299):793–797PubMedCrossRef
97.
go back to reference Ikeda H, Old LJ, Schreiber RD (2002) The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev 13(2):95–109PubMedCrossRef Ikeda H, Old LJ, Schreiber RD (2002) The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev 13(2):95–109PubMedCrossRef
98.
go back to reference Dighe AS, Richards E, Old LJ, Schreiber RD (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1(6):447–456PubMedCrossRef Dighe AS, Richards E, Old LJ, Schreiber RD (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1(6):447–456PubMedCrossRef
99.
go back to reference Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95(13):7556–7561PubMedCrossRef Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95(13):7556–7561PubMedCrossRef
100.
go back to reference Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97(1):192–197PubMedCrossRef Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97(1):192–197PubMedCrossRef
101.
go back to reference Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410(6832):1107–1111PubMedCrossRef Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410(6832):1107–1111PubMedCrossRef
102.
go back to reference Qin Z, Blankenstein T (2004) A cancer immunosurveillance controversy. Nat Immunol 5 (1):3-4 (author reply 4–5) Qin Z, Blankenstein T (2004) A cancer immunosurveillance controversy. Nat Immunol 5 (1):3-4 (author reply 4–5)
103.
go back to reference Schreiber TH, Podack ER (2009) A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas. Br J Cancer 101(3):381–386PubMedCrossRef Schreiber TH, Podack ER (2009) A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas. Br J Cancer 101(3):381–386PubMedCrossRef
104.
go back to reference Schreiber RD, Celada A, Buchmeier N (1986) The role of interferon-gamma in the induction of activated macrophages. Ann Inst Pasteur Immunol 137C(2):203–206PubMedCrossRef Schreiber RD, Celada A, Buchmeier N (1986) The role of interferon-gamma in the induction of activated macrophages. Ann Inst Pasteur Immunol 137C(2):203–206PubMedCrossRef
105.
go back to reference Dighe AS, Campbell D, Hsieh CS, Clarke S, Greaves DR, Gordon S, Murphy KM, Schreiber RD (1995) Tissue-specific targeting of cytokine unresponsiveness in transgenic mice. Immunity 3(5):657–666PubMedCrossRef Dighe AS, Campbell D, Hsieh CS, Clarke S, Greaves DR, Gordon S, Murphy KM, Schreiber RD (1995) Tissue-specific targeting of cytokine unresponsiveness in transgenic mice. Immunity 3(5):657–666PubMedCrossRef
106.
go back to reference Murphy TL, Cleveland MG, Kulesza P, Magram J, Murphy KM (1995) Regulation of interleukin 12 p40 expression through an NF-kappa B half-site. Mol Cell Biol 15(10):5258–5267PubMed Murphy TL, Cleveland MG, Kulesza P, Magram J, Murphy KM (1995) Regulation of interleukin 12 p40 expression through an NF-kappa B half-site. Mol Cell Biol 15(10):5258–5267PubMed
107.
go back to reference Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A (1999) Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 163(9):4647–4650PubMed Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A (1999) Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 163(9):4647–4650PubMed
108.
go back to reference Eberl G, MacDonald HR (2000) Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. Eur J Immunol 30(4):985–992PubMedCrossRef Eberl G, MacDonald HR (2000) Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. Eur J Immunol 30(4):985–992PubMedCrossRef
109.
go back to reference Badovinac VP, Tvinnereim AR, Harty JT (2000) Regulation of antigen-specific CD8 + T cell homeostasis by perforin and interferon-gamma. Science 290(5495):1354–1358PubMedCrossRef Badovinac VP, Tvinnereim AR, Harty JT (2000) Regulation of antigen-specific CD8 + T cell homeostasis by perforin and interferon-gamma. Science 290(5495):1354–1358PubMedCrossRef
110.
go back to reference Whitmire JK, Tan JT, Whitton JL (2005) Interferon-gamma acts directly on CD8 + T cells to increase their abundance during virus infection. J Exp Med 201(7):1053–1059PubMedCrossRef Whitmire JK, Tan JT, Whitton JL (2005) Interferon-gamma acts directly on CD8 + T cells to increase their abundance during virus infection. J Exp Med 201(7):1053–1059PubMedCrossRef
111.
go back to reference Bradley LM, Dalton DK, Croft M (1996) A direct role for IFN-gamma in regulation of Th1 cell development. J Immunol 157(4):1350–1358PubMed Bradley LM, Dalton DK, Croft M (1996) A direct role for IFN-gamma in regulation of Th1 cell development. J Immunol 157(4):1350–1358PubMed
112.
go back to reference Scott P (1991) IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. J Immunol 147(9):3149–3155PubMed Scott P (1991) IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. J Immunol 147(9):3149–3155PubMed
113.
go back to reference Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W (2009) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141–1149PubMedCrossRef Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G, Liu R, Zou W (2009) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141–1149PubMedCrossRef
114.
go back to reference Fallarino F, Gajewski TF (1999) Cutting edge: differentiation of antitumor CTL in vivo requires host expression of Stat1. J Immunol 163(8):4109–4113PubMed Fallarino F, Gajewski TF (1999) Cutting edge: differentiation of antitumor CTL in vivo requires host expression of Stat1. J Immunol 163(8):4109–4113PubMed
115.
go back to reference Kacha AK, Fallarino F, Markiewicz MA, Gajewski TF (2000) Cutting edge: spontaneous rejection of poorly immunogenic P1. HTR tumors by Stat6-deficient mice. J Immunol 165(11):6024–6028PubMed Kacha AK, Fallarino F, Markiewicz MA, Gajewski TF (2000) Cutting edge: spontaneous rejection of poorly immunogenic P1. HTR tumors by Stat6-deficient mice. J Immunol 165(11):6024–6028PubMed
116.
go back to reference Cao X, Leonard K, Collins LI, Cai SF, Mayer JC, Payton JE, Walter MJ, Piwnica-Worms D, Schreiber RD, Ley TJ (2009) Interleukin 12 stimulates IFN-gamma-mediated inhibition of tumor-induced regulatory T-cell proliferation and enhances tumor clearance. Cancer Res 69(22):8700–8709PubMedCrossRef Cao X, Leonard K, Collins LI, Cai SF, Mayer JC, Payton JE, Walter MJ, Piwnica-Worms D, Schreiber RD, Ley TJ (2009) Interleukin 12 stimulates IFN-gamma-mediated inhibition of tumor-induced regulatory T-cell proliferation and enhances tumor clearance. Cancer Res 69(22):8700–8709PubMedCrossRef
117.
go back to reference Luster AD, Ravetch JV (1987) Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med 166(4):1084–1097PubMedCrossRef Luster AD, Ravetch JV (1987) Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med 166(4):1084–1097PubMedCrossRef
118.
go back to reference Luster AD, Leder P (1993) IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo. J Exp Med 178(3):1057–1065PubMedCrossRef Luster AD, Leder P (1993) IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo. J Exp Med 178(3):1057–1065PubMedCrossRef
119.
go back to reference Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8(6):467–477PubMedCrossRef Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8(6):467–477PubMedCrossRef
120.
go back to reference Wu K, Kryczek I, Chen L, Zou W, Welling TH (2009) Kupffer cell suppression of CD8 + T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions. Cancer Res 69(20):8067–8075PubMedCrossRef Wu K, Kryczek I, Chen L, Zou W, Welling TH (2009) Kupffer cell suppression of CD8 + T cells in human hepatocellular carcinoma is mediated by B7-H1/programmed death-1 interactions. Cancer Res 69(20):8067–8075PubMedCrossRef
121.
go back to reference Wiendl H, Mitsdoerffer M, Schneider D, Chen L, Lochmuller H, Melms A, Weller M (2003) Human muscle cells express a B7-related molecule, B7-H1, with strong negative immune regulatory potential: a novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies. FASEB J 17(13):1892–1894PubMed Wiendl H, Mitsdoerffer M, Schneider D, Chen L, Lochmuller H, Melms A, Weller M (2003) Human muscle cells express a B7-related molecule, B7-H1, with strong negative immune regulatory potential: a novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies. FASEB J 17(13):1892–1894PubMed
122.
go back to reference Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800PubMed Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800PubMed
123.
go back to reference Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, Saudemont A, Quesnel B (2007) Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood 110(1):296–304PubMedCrossRef Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, Saudemont A, Quesnel B (2007) Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood 110(1):296–304PubMedCrossRef
124.
go back to reference Kondo A, Yamashita T, Tamura H, Zhao W, Tsuji T, Shimizu M, Shinya E, Takahashi H, Tamada K, Chen L, Dan K, Ogata K (2010) Interferon-gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes. Blood 116(7):1124–1131PubMedCrossRef Kondo A, Yamashita T, Tamura H, Zhao W, Tsuji T, Shimizu M, Shinya E, Takahashi H, Tamada K, Chen L, Dan K, Ogata K (2010) Interferon-gamma and tumor necrosis factor-alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes. Blood 116(7):1124–1131PubMedCrossRef
125.
go back to reference Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL (2002) Potential regulatory function of human dendritic cells expressing indoleamine 2, 3-dioxygenase. Science 297(5588):1867–1870PubMedCrossRef Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL (2002) Potential regulatory function of human dendritic cells expressing indoleamine 2, 3-dioxygenase. Science 297(5588):1867–1870PubMedCrossRef
126.
go back to reference Carlin JM, Borden EC, Sondel PM, Byrne GI (1987) Biologic-response-modifier-induced indoleamine 2, 3-dioxygenase activity in human peripheral blood mononuclear cell cultures. J Immunol 139(7):2414–2418PubMed Carlin JM, Borden EC, Sondel PM, Byrne GI (1987) Biologic-response-modifier-induced indoleamine 2, 3-dioxygenase activity in human peripheral blood mononuclear cell cultures. J Immunol 139(7):2414–2418PubMed
127.
go back to reference Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5(4):263–274PubMedCrossRef Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5(4):263–274PubMedCrossRef
128.
go back to reference Mellor AL, Munn DH (2008) Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol 8(1):74–80PubMedCrossRef Mellor AL, Munn DH (2008) Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol 8(1):74–80PubMedCrossRef
129.
go back to reference Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC (2005) Inhibition of indoleamine 2, 3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 11(3):312–319PubMedCrossRef Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC (2005) Inhibition of indoleamine 2, 3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 11(3):312–319PubMedCrossRef
130.
go back to reference Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH (2007) Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase. J Clin Invest 117(9):2570–2582PubMedCrossRef Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH (2007) Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2, 3-dioxygenase. J Clin Invest 117(9):2570–2582PubMedCrossRef
131.
go back to reference Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti P (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 4(12):1206–1212PubMedCrossRef Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti P (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 4(12):1206–1212PubMedCrossRef
132.
go back to reference Muller AJ, Sharma MD, Chandler PR, Duhadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL (2008) Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2, 3 dioxygenase. Proc Natl Acad Sci USA 105(44):17073–17078PubMedCrossRef Muller AJ, Sharma MD, Chandler PR, Duhadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL (2008) Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2, 3 dioxygenase. Proc Natl Acad Sci USA 105(44):17073–17078PubMedCrossRef
133.
go back to reference Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG, Ochoa JB, Ochoa AC (2003) l-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol 171(3):1232–1239PubMed Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG, Ochoa JB, Ochoa AC (2003) l-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol 171(3):1232–1239PubMed
134.
go back to reference Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, Delgado A, Correa P, Brayer J, Sotomayor EM, Antonia S, Ochoa JB, Ochoa AC (2004) Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 64(16):5839–5849PubMedCrossRef Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, Delgado A, Correa P, Brayer J, Sotomayor EM, Antonia S, Ochoa JB, Ochoa AC (2004) Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 64(16):5839–5849PubMedCrossRef
135.
go back to reference Saio M, Radoja S, Marino M, Frey AB (2001) Tumor-infiltrating macrophages induce apoptosis in activated CD8(+) T cells by a mechanism requiring cell contact and mediated by both the cell-associated form of TNF and nitric oxide. J Immunol 167(10):5583–5593PubMed Saio M, Radoja S, Marino M, Frey AB (2001) Tumor-infiltrating macrophages induce apoptosis in activated CD8(+) T cells by a mechanism requiring cell contact and mediated by both the cell-associated form of TNF and nitric oxide. J Immunol 167(10):5583–5593PubMed
136.
go back to reference Kusmartsev SA, Li Y, Chen SH (2000) Gr-1 + myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J Immunol 165(2):779–785PubMed Kusmartsev SA, Li Y, Chen SH (2000) Gr-1 + myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J Immunol 165(2):779–785PubMed
137.
go back to reference Liscovsky MV, Ranocchia RP, Gorlino CV, Alignani DO, Moron G, Maletto BA, Pistoresi-Palencia MC (2009) Interferon-gamma priming is involved in the activation of arginase by oligodeoxinucleotides containing CpG motifs in murine macrophages. Immunology 128(1 Suppl):e159–e169PubMedCrossRef Liscovsky MV, Ranocchia RP, Gorlino CV, Alignani DO, Moron G, Maletto BA, Pistoresi-Palencia MC (2009) Interferon-gamma priming is involved in the activation of arginase by oligodeoxinucleotides containing CpG motifs in murine macrophages. Immunology 128(1 Suppl):e159–e169PubMedCrossRef
138.
go back to reference Mazzoni A, Bronte V, Visintin A, Spitzer JH, Apolloni E, Serafini P, Zanovello P, Segal DM (2002) Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol 168(2):689–695PubMed Mazzoni A, Bronte V, Visintin A, Spitzer JH, Apolloni E, Serafini P, Zanovello P, Segal DM (2002) Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol 168(2):689–695PubMed
139.
go back to reference Modolell M, Corraliza IM, Link F, Soler G, Eichmann K (1995) Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH1 and TH2 cytokines. Eur J Immunol 25(4):1101–1104PubMedCrossRef Modolell M, Corraliza IM, Link F, Soler G, Eichmann K (1995) Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH1 and TH2 cytokines. Eur J Immunol 25(4):1101–1104PubMedCrossRef
140.
go back to reference Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, Pearce EJ, Wynn TA (2001) Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of l-arginine metabolism. J Immunol 167(11):6533–6544PubMed Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, Pearce EJ, Wynn TA (2001) Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of l-arginine metabolism. J Immunol 167(11):6533–6544PubMed
141.
go back to reference Norian LA, Rodriguez PC, O’Mara LA, Zabaleta J, Ochoa AC, Cella M, Allen PM (2009) Tumor-infiltrating regulatory dendritic cells inhibit CD8 + T cell function via l-arginine metabolism. Cancer Res 69(7):3086–3094PubMedCrossRef Norian LA, Rodriguez PC, O’Mara LA, Zabaleta J, Ochoa AC, Cella M, Allen PM (2009) Tumor-infiltrating regulatory dendritic cells inhibit CD8 + T cell function via l-arginine metabolism. Cancer Res 69(7):3086–3094PubMedCrossRef
142.
go back to reference Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O’Neill A, Mier J, Ochoa AC (2005) Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 65(8):3044–3048PubMed Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O’Neill A, Mier J, Ochoa AC (2005) Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 65(8):3044–3048PubMed
143.
go back to reference Ochoa AC, Zea AH, Hernandez C, Rodriguez PC (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13(2 Pt 2):721s–726sPubMedCrossRef Ochoa AC, Zea AH, Hernandez C, Rodriguez PC (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13(2 Pt 2):721s–726sPubMedCrossRef
144.
go back to reference Rodriguez PC, Ochoa AC (2008) Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev 222:180–191PubMedCrossRef Rodriguez PC, Ochoa AC (2008) Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev 222:180–191PubMedCrossRef
145.
go back to reference Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69(4):1553–1560PubMedCrossRef Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69(4):1553–1560PubMedCrossRef
146.
go back to reference Highfill SL, Rodriguez PC, Zhou Q, Goetz CA, Koehn BH, Veenstra R, Taylor PA, Panoskaltsis-Mortari A, Serody JS, Munn DH, Tolar J, Ochoa AC, Blazar BR (2010) Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13. Blood 116(25):5738–5747PubMedCrossRef Highfill SL, Rodriguez PC, Zhou Q, Goetz CA, Koehn BH, Veenstra R, Taylor PA, Panoskaltsis-Mortari A, Serody JS, Munn DH, Tolar J, Ochoa AC, Blazar BR (2010) Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13. Blood 116(25):5738–5747PubMedCrossRef
147.
go back to reference Ilangumaran S, Rottapel R (2003) Regulation of cytokine receptor signaling by SOCS1. Immunol Rev 192:196–211PubMedCrossRef Ilangumaran S, Rottapel R (2003) Regulation of cytokine receptor signaling by SOCS1. Immunol Rev 192:196–211PubMedCrossRef
148.
go back to reference Starr R, Fuchsberger M, Lau LS, Uldrich AP, Goradia A, Willson TA, Verhagen AM, Alexander WS, Smyth MJ (2009) SOCS-1 binding to tyrosine 441 of IFN-gamma receptor subunit 1 contributes to the attenuation of IFN-gamma signaling in vivo. J Immunol 183(7):4537–4544PubMedCrossRef Starr R, Fuchsberger M, Lau LS, Uldrich AP, Goradia A, Willson TA, Verhagen AM, Alexander WS, Smyth MJ (2009) SOCS-1 binding to tyrosine 441 of IFN-gamma receptor subunit 1 contributes to the attenuation of IFN-gamma signaling in vivo. J Immunol 183(7):4537–4544PubMedCrossRef
149.
go back to reference Taniguchi K, Petersson M, Hoglund P, Kiessling R, Klein G, Karre K (1987) Interferon gamma induces lung colonization by intravenously inoculated B16 melanoma cells in parallel with enhanced expression of class I major histocompatibility complex antigens. Proc Natl Acad Sci USA 84(10):3405–3409PubMedCrossRef Taniguchi K, Petersson M, Hoglund P, Kiessling R, Klein G, Karre K (1987) Interferon gamma induces lung colonization by intravenously inoculated B16 melanoma cells in parallel with enhanced expression of class I major histocompatibility complex antigens. Proc Natl Acad Sci USA 84(10):3405–3409PubMedCrossRef
150.
go back to reference Cho HI, Lee YR, Celis E (2010) Interferon gamma limits the effectiveness of melanoma peptide vaccines. Blood Cho HI, Lee YR, Celis E (2010) Interferon gamma limits the effectiveness of melanoma peptide vaccines. Blood
151.
go back to reference Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin AL, Monsarrat B, Van Velthoven R, Cerottini JC, Boon T, Gairin JE, Van den Eynde BJ (2000) Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity 12(1):107–117PubMedCrossRef Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin AL, Monsarrat B, Van Velthoven R, Cerottini JC, Boon T, Gairin JE, Van den Eynde BJ (2000) Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity 12(1):107–117PubMedCrossRef
152.
go back to reference Gobin SJ, van den Elsen PJ (2000) Transcriptional regulation of the MHC class Ib genes HLA-E, HLA-F, and HLA-G. Hum Immunol 61(11):1102–1107PubMedCrossRef Gobin SJ, van den Elsen PJ (2000) Transcriptional regulation of the MHC class Ib genes HLA-E, HLA-F, and HLA-G. Hum Immunol 61(11):1102–1107PubMedCrossRef
153.
go back to reference Zaidi MR, Davis S, Noonan FP, Graff-Cherry C, Hawley TS, Walker RL, Feigenbaum L, Fuchs E, Lyakh L, Young HA, Hornyak TJ, Arnheiter H, Trinchieri G, Meltzer PS, De Fabo EC, Merlino G (2011) Interferon-gamma links ultraviolet radiation to melanomagenesis in mice. Nature 469(7331):548–553PubMedCrossRef Zaidi MR, Davis S, Noonan FP, Graff-Cherry C, Hawley TS, Walker RL, Feigenbaum L, Fuchs E, Lyakh L, Young HA, Hornyak TJ, Arnheiter H, Trinchieri G, Meltzer PS, De Fabo EC, Merlino G (2011) Interferon-gamma links ultraviolet radiation to melanomagenesis in mice. Nature 469(7331):548–553PubMedCrossRef
154.
go back to reference Berner V, Liu H, Zhou Q, Alderson KL, Sun K, Weiss JM, Back TC, Longo DL, Blazar BR, Wiltrout RH, Welniak LA, Redelman D, Murphy WJ (2007) IFN-gamma mediates CD4 + T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy. Nat Med 13(3):354–360PubMedCrossRef Berner V, Liu H, Zhou Q, Alderson KL, Sun K, Weiss JM, Back TC, Longo DL, Blazar BR, Wiltrout RH, Welniak LA, Redelman D, Murphy WJ (2007) IFN-gamma mediates CD4 + T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy. Nat Med 13(3):354–360PubMedCrossRef
155.
go back to reference Garbe C, Krasagakis K, Zouboulis CC, Schroder K, Kruger S, Stadler R, Orfanos CE (1990) Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype. J Invest Dermatol 95(6 Suppl):231S–237SPubMedCrossRef Garbe C, Krasagakis K, Zouboulis CC, Schroder K, Kruger S, Stadler R, Orfanos CE (1990) Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype. J Invest Dermatol 95(6 Suppl):231S–237SPubMedCrossRef
156.
go back to reference Creagan ET, Ahmann DL, Long HJ, Frytak S, Sherwin SA, Chang MN (1987) Phase II study of recombinant interferon-gamma in patients with disseminated malignant melanoma. Cancer Treat Rep 71(9):843–844PubMed Creagan ET, Ahmann DL, Long HJ, Frytak S, Sherwin SA, Chang MN (1987) Phase II study of recombinant interferon-gamma in patients with disseminated malignant melanoma. Cancer Treat Rep 71(9):843–844PubMed
157.
go back to reference Ernstoff MS, Trautman T, Davis CA, Reich SD, Witman P, Balser J, Rudnick S, Kirkwood JM (1987) A randomized phase I/II study of continuous versus intermittent intravenous interferon gamma in patients with metastatic melanoma. J Clin Oncol 5(11):1804–1810PubMed Ernstoff MS, Trautman T, Davis CA, Reich SD, Witman P, Balser J, Rudnick S, Kirkwood JM (1987) A randomized phase I/II study of continuous versus intermittent intravenous interferon gamma in patients with metastatic melanoma. J Clin Oncol 5(11):1804–1810PubMed
158.
go back to reference Kopp WC, Smith JW II, Ewel CH, Alvord WG, Main C, Guyre PM, Steis RG, Longo DL, Urba WJ (1993) Immunomodulatory effects of interferon-gamma in patients with metastatic malignant melanoma. J Immunother Emphas Tumor Immunol 13(3):181–190 Kopp WC, Smith JW II, Ewel CH, Alvord WG, Main C, Guyre PM, Steis RG, Longo DL, Urba WJ (1993) Immunomodulatory effects of interferon-gamma in patients with metastatic malignant melanoma. J Immunother Emphas Tumor Immunol 13(3):181–190
159.
go back to reference Kowalzick L, Weyer U, Lange P, Breitbart EW (1990) Systemic therapy of advanced metastatic malignant melanoma with a combination of fibroblast interferon-beta and recombinant interferon-gamma. Dermatologica 181(4):298–303PubMedCrossRef Kowalzick L, Weyer U, Lange P, Breitbart EW (1990) Systemic therapy of advanced metastatic malignant melanoma with a combination of fibroblast interferon-beta and recombinant interferon-gamma. Dermatologica 181(4):298–303PubMedCrossRef
160.
go back to reference Meyskens FL Jr, Kopecky K, Samson M, Hersh E, Macdonald J, Jaffe H, Crowley J, Coltman C (1990) Recombinant human interferon gamma: adverse effects in high-risk stage I and II cutaneous malignant melanoma. J Natl Cancer Inst 82(12):1071PubMed Meyskens FL Jr, Kopecky K, Samson M, Hersh E, Macdonald J, Jaffe H, Crowley J, Coltman C (1990) Recombinant human interferon gamma: adverse effects in high-risk stage I and II cutaneous malignant melanoma. J Natl Cancer Inst 82(12):1071PubMed
161.
go back to reference Meyskens FL Jr, Kopecky KJ, Taylor CW, Noyes RD, Tuthill RJ, Hersh EM, Feun LG, Doroshow JH, Flaherty LE, Sondak VK (1995) Randomized trial of adjuvant human interferon gamma versus observation in high-risk cutaneous melanoma: a southwest oncology group study. J Natl Cancer Inst 87(22):1710–1713PubMedCrossRef Meyskens FL Jr, Kopecky KJ, Taylor CW, Noyes RD, Tuthill RJ, Hersh EM, Feun LG, Doroshow JH, Flaherty LE, Sondak VK (1995) Randomized trial of adjuvant human interferon gamma versus observation in high-risk cutaneous melanoma: a southwest oncology group study. J Natl Cancer Inst 87(22):1710–1713PubMedCrossRef
162.
go back to reference Coughlin CM, Salhany KE, Gee MS, LaTemple DC, Kotenko S, Ma X, Gri G, Wysocka M, Kim JE, Liu L, Liao F, Farber JM, Pestka S, Trinchieri G, Lee WM (1998) Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity 9(1):25–34PubMedCrossRef Coughlin CM, Salhany KE, Gee MS, LaTemple DC, Kotenko S, Ma X, Gri G, Wysocka M, Kim JE, Liu L, Liao F, Farber JM, Pestka S, Trinchieri G, Lee WM (1998) Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity 9(1):25–34PubMedCrossRef
163.
go back to reference Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto Y, Fu XY (1996) Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1. Science 272(5262):719–722PubMedCrossRef Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto Y, Fu XY (1996) Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1. Science 272(5262):719–722PubMedCrossRef
164.
go back to reference Bromberg JF, Horvath CM, Wen Z, Schreiber RD, Darnell JE Jr (1996) Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. Proc Natl Acad Sci USA 93(15):7673–7678PubMedCrossRef Bromberg JF, Horvath CM, Wen Z, Schreiber RD, Darnell JE Jr (1996) Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. Proc Natl Acad Sci USA 93(15):7673–7678PubMedCrossRef
165.
go back to reference Sgadari C, Angiolillo AL, Cherney BW, Pike SE, Farber JM, Koniaris LG, Vanguri P, Burd PR, Sheikh N, Gupta G, Teruya-Feldstein J, Tosato G (1996) Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo. Proc Natl Acad Sci USA 93(24):13791–13796PubMedCrossRef Sgadari C, Angiolillo AL, Cherney BW, Pike SE, Farber JM, Koniaris LG, Vanguri P, Burd PR, Sheikh N, Gupta G, Teruya-Feldstein J, Tosato G (1996) Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo. Proc Natl Acad Sci USA 93(24):13791–13796PubMedCrossRef
166.
go back to reference Arenberg DA, Kunkel SL, Polverini PJ, Morris SB, Burdick MD, Glass MC, Taub DT, Iannettoni MD, Whyte RI, Strieter RM (1996) Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J Exp Med 184(3):981–992PubMedCrossRef Arenberg DA, Kunkel SL, Polverini PJ, Morris SB, Burdick MD, Glass MC, Taub DT, Iannettoni MD, Whyte RI, Strieter RM (1996) Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J Exp Med 184(3):981–992PubMedCrossRef
167.
go back to reference Sgadari C, Farber JM, Angiolillo AL, Liao F, Teruya-Feldstein J, Burd PR, Yao L, Gupta G, Kanegane C, Tosato G (1997) Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo. Blood 89(8):2635–2643PubMed Sgadari C, Farber JM, Angiolillo AL, Liao F, Teruya-Feldstein J, Burd PR, Yao L, Gupta G, Kanegane C, Tosato G (1997) Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo. Blood 89(8):2635–2643PubMed
168.
go back to reference Coughlin CM, Salhany KE, Wysocka M, Aruga E, Kurzawa H, Chang AE, Hunter CA, Fox JC, Trinchieri G, Lee WM (1998) Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest 101(6):1441–1452PubMedCrossRef Coughlin CM, Salhany KE, Wysocka M, Aruga E, Kurzawa H, Chang AE, Hunter CA, Fox JC, Trinchieri G, Lee WM (1998) Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest 101(6):1441–1452PubMedCrossRef
169.
go back to reference Briesemeister D, Sommermeyer D, Loddenkemper C, Loew R, Uckert W, Blankenstein T, Kammertoens T (2011) Tumor rejection by local interferon gamma induction in established tumors is associated with blood vessel destruction and necrosis. Int J Cancer 128(2):371–378PubMedCrossRef Briesemeister D, Sommermeyer D, Loddenkemper C, Loew R, Uckert W, Blankenstein T, Kammertoens T (2011) Tumor rejection by local interferon gamma induction in established tumors is associated with blood vessel destruction and necrosis. Int J Cancer 128(2):371–378PubMedCrossRef
170.
go back to reference Groux H, Bigler M, de Vries JE, Roncarolo MG (1998) Inhibitory and stimulatory effects of IL-10 on human CD8 + T cells. J Immunol 160(7):3188–3193PubMed Groux H, Bigler M, de Vries JE, Roncarolo MG (1998) Inhibitory and stimulatory effects of IL-10 on human CD8 + T cells. J Immunol 160(7):3188–3193PubMed
Metadata
Title
Dual biological effects of the cytokines interleukin-10 and interferon-γ
Authors
Cailin Moira Wilke
Shuang Wei
Lin Wang
Ilona Kryczek
John Kao
Weiping Zou
Publication date
01-11-2011
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 11/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-011-1104-5

Other articles of this Issue 11/2011

Cancer Immunology, Immunotherapy 11/2011 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine