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Published in: Cancer Immunology, Immunotherapy 6/2004

01-06-2004 | Original Article

Dendritic cells are dysfunctional in patients with operable breast cancer

Authors: Sukchai Satthaporn, Adrian Robins, Wichai Vassanasiri, Mohamed El-Sheemy, Jibril A Jibril, David Clark, David Valerio, Oleg Eremin

Published in: Cancer Immunology, Immunotherapy | Issue 6/2004

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Abstract

Background: Dendritic cells (DCs) play a crucial role in presenting antigens to T lymphocytes and inducing cytotoxic T cells. DCs have been studied in patients with breast cancer to define the factors leading to failure of an effective systemic and locoregional anticancer host response. Methods: Purified DCs were obtained from peripheral blood (PB) and lymph nodes (LNs) of women with operable breast cancer, using immunomagnetic bead selection. The stimulatory capacity of DCs in the allogeneic mixed leukocyte reaction (MLR) and autologous T cell proliferation test (purified protein derivative (PPD) as stimulator), the expression of surface markers on DCs and the production of cytokines in vitro by DCs from patients with operable breast cancer and from healthy donors (controls) were studied. Results: 70–75% purified DCs were isolated from PB and LNs. PBDCs and LNDCs from patients with operable breast cancer demonstrated a reduced capacity to stimulate in an MLR, compared with PBDCs from normal donors (p<0.01). Autologous T cell proliferation in patients had a decreased ability to respond to PPD, when compared with controls (p<0.01). However, T cells from patients responded as well as control T lymphocytes in the presence of control DCs. PBDCs and LNDCs from patients expressed low levels of HLA-DR and CD86, and induced decreased interleukin-12 (IL-12) secretion in vitro, compared with DCs from normal donors (p<0.01). Conclusion: These data suggest a defective DC function in patients with operable breast cancer. Switched-off DCs in patients with early breast cancer and decreased IL-12 production may be important factors for progressive tumour growth.
Literature
1.
go back to reference Almand B, Resser JR, Lindman B et al (2000) Clinical significance of defective dendritic cell differentiation in cancer [in process citation]. Clin Cancer Res 6(5):1755PubMed Almand B, Resser JR, Lindman B et al (2000) Clinical significance of defective dendritic cell differentiation in cancer [in process citation]. Clin Cancer Res 6(5):1755PubMed
2.
go back to reference Al-Sarireh B, Robins O, Eremin O (2000) Mononuclear phagocytes but not tumour cells are the main source of elevated interleukin (IL)-10 levels in human breast cancer. J R Coll Surg Edinb 46(1):92 Al-Sarireh B, Robins O, Eremin O (2000) Mononuclear phagocytes but not tumour cells are the main source of elevated interleukin (IL)-10 levels in human breast cancer. J R Coll Surg Edinb 46(1):92
3.
go back to reference Anton D, Dabadghao S, Palucka K et al (1998) Generation of dendritic cells from peripheral blood adherent cells in medium with human serum. Scand J Immunol 47(2):116PubMed Anton D, Dabadghao S, Palucka K et al (1998) Generation of dendritic cells from peripheral blood adherent cells in medium with human serum. Scand J Immunol 47(2):116PubMed
4.
5.
go back to reference Beissert S, Hosoi J, Grabbe S et al (1995) IL-10 inhibits tumor antigen presentation by epidermal antigen- presenting cells. J Immunol 154(3):1280PubMed Beissert S, Hosoi J, Grabbe S et al (1995) IL-10 inhibits tumor antigen presentation by epidermal antigen- presenting cells. J Immunol 154(3):1280PubMed
6.
go back to reference Bianchi R, Grohmann U, Vacca C et al (1999) Autocrine IL-12 is involved in dendritic cell modulation via CD40 ligation. J Immunol 163(5):2517PubMed Bianchi R, Grohmann U, Vacca C et al (1999) Autocrine IL-12 is involved in dendritic cell modulation via CD40 ligation. J Immunol 163(5):2517PubMed
7.
go back to reference Brooks CF, Moore M (1988) Differential MHC class II expression on human peripheral blood monocytes and dendritic cells. Immunology 63(2):303PubMed Brooks CF, Moore M (1988) Differential MHC class II expression on human peripheral blood monocytes and dendritic cells. Immunology 63(2):303PubMed
8.
go back to reference Buelens C, Verhasselt V, De Groote D et al (1997) Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor. Eur J Immunol 27(3):756PubMed Buelens C, Verhasselt V, De Groote D et al (1997) Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor. Eur J Immunol 27(3):756PubMed
9.
go back to reference Chang JW, Vaquerano JE, Zhou YM et al (1999) Characterization of dendritic cells generated from peripheral blood of patients with malignant melanoma. Anticancer Res 19(3A):1815PubMed Chang JW, Vaquerano JE, Zhou YM et al (1999) Characterization of dendritic cells generated from peripheral blood of patients with malignant melanoma. Anticancer Res 19(3A):1815PubMed
10.
go back to reference Chao D, Bahl P, Houlbrook S et al (1999) Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay. Br J Cancer 81(8):1280CrossRefPubMed Chao D, Bahl P, Houlbrook S et al (1999) Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay. Br J Cancer 81(8):1280CrossRefPubMed
11.
go back to reference Chaux P, Moutet M, Faivre J et al (1996) Inflammatory cells infiltrating human colorectal carcinomas express HLA class II but not B7-1 and B7-2 costimulatory molecules of the T-cell activation. Lab Invest 74(5):975PubMed Chaux P, Moutet M, Faivre J et al (1996) Inflammatory cells infiltrating human colorectal carcinomas express HLA class II but not B7-1 and B7-2 costimulatory molecules of the T-cell activation. Lab Invest 74(5):975PubMed
12.
go back to reference Chen B, Shi Y, Smith JD, Choi D (1998) The role of tumor necrosis factor-alpha in modulating the quantity of peripheral blood-derived, cytokine-driven human dendritic cells and its role in enhancing the quality of dendritic cell function in presenting soluble antigens to CD4+ T cells in vitro. Blood 91(12):4652PubMed Chen B, Shi Y, Smith JD, Choi D (1998) The role of tumor necrosis factor-alpha in modulating the quantity of peripheral blood-derived, cytokine-driven human dendritic cells and its role in enhancing the quality of dendritic cell function in presenting soluble antigens to CD4+ T cells in vitro. Blood 91(12):4652PubMed
13.
go back to reference Clare-Salzler MJ, Brooks J, Chai A et al (1992) Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer. J Clin Invest 90(3):741PubMed Clare-Salzler MJ, Brooks J, Chai A et al (1992) Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer. J Clin Invest 90(3):741PubMed
14.
go back to reference CRC (2001) Information document. Cancer Research UK, London CRC (2001) Information document. Cancer Research UK, London
15.
go back to reference Damiani D, Stocchi R, Masolini P et al (2002) Dendritic cell recovery after autologous stem cell transplantation. Bone Marrow Transplant 30(5):261CrossRefPubMed Damiani D, Stocchi R, Masolini P et al (2002) Dendritic cell recovery after autologous stem cell transplantation. Bone Marrow Transplant 30(5):261CrossRefPubMed
16.
go back to reference De Smedt T, Van Mechelen M, De Becker G et al (1997) Effect of interleukin-10 on dendritic cell maturation and function. Eur J Immunol 27(5):1229PubMed De Smedt T, Van Mechelen M, De Becker G et al (1997) Effect of interleukin-10 on dendritic cell maturation and function. Eur J Immunol 27(5):1229PubMed
17.
go back to reference Enk AH, Angeloni VL, Udey MC, Katz SI (1993) Inhibition of Langerhans cell antigen-presenting function by IL-10: a role for IL-10 in induction of tolerance. J Immunol 151(5):2390PubMed Enk AH, Angeloni VL, Udey MC, Katz SI (1993) Inhibition of Langerhans cell antigen-presenting function by IL-10: a role for IL-10 in induction of tolerance. J Immunol 151(5):2390PubMed
18.
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):309PubMed 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):309PubMed
19.
go back to reference Gabrilovich DI, Patterson S, Harvey JJ et al (1995) Defects in the function of dendritic cells in murine retroviral infection. Adv Exp Med Biol 378:469PubMed Gabrilovich DI, Patterson S, Harvey JJ et al (1995) Defects in the function of dendritic cells in murine retroviral infection. Adv Exp Med Biol 378:469PubMed
20.
go back to reference Gabrilovich DI, Ciernik IF, Carbone DP (1996) Dendritic cells in antitumor immune responses, I: defective antigen presentation in tumor-bearing hosts. Cell Immunol 170(1):101CrossRefPubMed Gabrilovich DI, Ciernik IF, Carbone DP (1996) Dendritic cells in antitumor immune responses, I: defective antigen presentation in tumor-bearing hosts. Cell Immunol 170(1):101CrossRefPubMed
21.
go back to reference Gabrilovich DI, Corak J, Ciernik IF et al (1997) Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res 3(3):483PubMed Gabrilovich DI, Corak J, Ciernik IF et al (1997) Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res 3(3):483PubMed
22.
go back to reference Garrity T, Pandit R, Wright MA et al (1997) Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells. Int J Cancer 73(5):663PubMed Garrity T, Pandit R, Wright MA et al (1997) Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells. Int J Cancer 73(5):663PubMed
23.
go back to reference Grufman P, Karre K (2000) Innate and adaptive immunity to tumors: IL-12 is required for optimal responses. Eur J Immunol 30(4):1088CrossRefPubMed Grufman P, Karre K (2000) Innate and adaptive immunity to tumors: IL-12 is required for optimal responses. Eur J Immunol 30(4):1088CrossRefPubMed
24.
go back to reference Hart DN (1997) Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 90(9):3245PubMed Hart DN (1997) Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 90(9):3245PubMed
25.
go back to reference Heufler C, Koch F, Stanzl U et al (1996) Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells. Eur J Immunol 26(3):659PubMed Heufler C, Koch F, Stanzl U et al (1996) Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells. Eur J Immunol 26(3):659PubMed
26.
go back to reference Huang YM, Xiao BG, Westerlund I, Link H (1999) Phenotypic and functional properties of dendritic cells isolated from human peripheral blood in comparison with mononuclear cells and T cells. Scand J Immunol 49(2):177CrossRefPubMed Huang YM, Xiao BG, Westerlund I, Link H (1999) Phenotypic and functional properties of dendritic cells isolated from human peripheral blood in comparison with mononuclear cells and T cells. Scand J Immunol 49(2):177CrossRefPubMed
27.
go back to reference Kabel PJ, de Haan-Meulman M, Voorbij HA et al (1989) Accessory cells with a morphology and marker pattern of dendritic cells can be obtained from elutriator-purified blood monocyte fractions: an enhancing effect of metrizamide in this differentiation. Immunobiology 179(4–5):395 Kabel PJ, de Haan-Meulman M, Voorbij HA et al (1989) Accessory cells with a morphology and marker pattern of dendritic cells can be obtained from elutriator-purified blood monocyte fractions: an enhancing effect of metrizamide in this differentiation. Immunobiology 179(4–5):395
28.
go back to reference Kelsall BL, Stuber E, Neurath M, Strober W (1996) Interleukin-12 production by dendritic cells: the role of CD40-CD40L interactions in Th1 T-cell responses. Ann N Y Acad Sci 795:116PubMed Kelsall BL, Stuber E, Neurath M, Strober W (1996) Interleukin-12 production by dendritic cells: the role of CD40-CD40L interactions in Th1 T-cell responses. Ann N Y Acad Sci 795:116PubMed
29.
go back to reference Knight SC (1986) Non-adherent, low density cells from human peripheral blood contain dendritic cells and monocytes, both with veiled morphology. Immunology 57:595PubMed Knight SC (1986) Non-adherent, low density cells from human peripheral blood contain dendritic cells and monocytes, both with veiled morphology. Immunology 57:595PubMed
30.
go back to reference Koch F, Stanzl U, Jennewein P et al (1996) High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10 [published erratum appears in J Exp Med (1996) 184(4):following 1590]. J Exp Med 184(2):741PubMed Koch F, Stanzl U, Jennewein P et al (1996) High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10 [published erratum appears in J Exp Med (1996) 184(4):following 1590]. J Exp Med 184(2):741PubMed
31.
go back to reference Labeur MS, Roters B, Pers B et al (1999) Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage. J Immunol 162(1):168PubMed Labeur MS, Roters B, Pers B et al (1999) Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage. J Immunol 162(1):168PubMed
32.
go back to reference Limpens J, Van Meijer M, Van Santen HM et al (1991) Alterations in dendritic cell phenotype and function associated with immunoenhancing effects of a subcutaneously administered cyclophosphamide derivative. Immunology 73(3):255 Limpens J, Van Meijer M, Van Santen HM et al (1991) Alterations in dendritic cell phenotype and function associated with immunoenhancing effects of a subcutaneously administered cyclophosphamide derivative. Immunology 73(3):255
33.
go back to reference Macatonia SE, Hosken NA, Litton M et al (1995) Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol 154(10):5071PubMed Macatonia SE, Hosken NA, Litton M et al (1995) Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol 154(10):5071PubMed
34.
go back to reference Markowicz S, Walewski J, Zajda K et al (2002) Recovery of dendritic cell counts and function in peripheral blood of cancer patients after chemotherapy. Cytokines Cell Mol Ther 7(1):15CrossRefPubMed Markowicz S, Walewski J, Zajda K et al (2002) Recovery of dendritic cell counts and function in peripheral blood of cancer patients after chemotherapy. Cytokines Cell Mol Ther 7(1):15CrossRefPubMed
35.
go back to reference Marsh J, Glick B (1992) The effect of cyclophosphamide on bursal and splenic dendritic cells. Poult Sci 71(1):113PubMed Marsh J, Glick B (1992) The effect of cyclophosphamide on bursal and splenic dendritic cells. Poult Sci 71(1):113PubMed
36.
go back to reference McLellan AD, Starling GC, Williams LA et al (1995) Activation of human peripheral blood dendritic cells induces the CD86 co-stimulatory molecule [published erratum appears in Eur J Immunol (1995) 25(12):3525]. Eur J Immunol 25(7):2064PubMed McLellan AD, Starling GC, Williams LA et al (1995) Activation of human peripheral blood dendritic cells induces the CD86 co-stimulatory molecule [published erratum appears in Eur J Immunol (1995) 25(12):3525]. Eur J Immunol 25(7):2064PubMed
37.
go back to reference Melero I, Duarte M, Ruiz J et al (1999) Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas. Gene Ther 6(10):1779CrossRefPubMed Melero I, Duarte M, Ruiz J et al (1999) Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas. Gene Ther 6(10):1779CrossRefPubMed
38.
go back to reference Ninomiya T, Akbar SM, Masumoto T et al (1999) Dendritic cells with immature phenotype and defective function in the peripheral blood from patients with hepatocellular carcinoma. J Hepatol 31(2):323CrossRefPubMed Ninomiya T, Akbar SM, Masumoto T et al (1999) Dendritic cells with immature phenotype and defective function in the peripheral blood from patients with hepatocellular carcinoma. J Hepatol 31(2):323CrossRefPubMed
39.
go back to reference Pardoll DM. Cancer vaccines (1998) Nat Med 4[Suppl 5]:525 Pardoll DM. Cancer vaccines (1998) Nat Med 4[Suppl 5]:525
40.
go back to reference Pawelec G, Zeuthen J, Kiessling R (1997) Escape from host-antitumor immunity. Crit Rev Oncog 8(2–3):111 Pawelec G, Zeuthen J, Kiessling R (1997) Escape from host-antitumor immunity. Crit Rev Oncog 8(2–3):111
41.
go back to reference Radmayr C, Bock G, Hobisch A et al (1995) Dendritic antigen-presenting cells from the peripheral blood of renal-cell-carcinoma patients. Int J Cancer 63(5):627PubMed Radmayr C, Bock G, Hobisch A et al (1995) Dendritic antigen-presenting cells from the peripheral blood of renal-cell-carcinoma patients. Int J Cancer 63(5):627PubMed
42.
go back to reference Ria F, Penna G, Adorini L (1998) Th1 cells induce and Th2 inhibit antigen-dependent IL-12 secretion by dendritic cells. Eur J Immunol 28(6):2003CrossRefPubMed Ria F, Penna G, Adorini L (1998) Th1 cells induce and Th2 inhibit antigen-dependent IL-12 secretion by dendritic cells. Eur J Immunol 28(6):2003CrossRefPubMed
43.
go back to reference Satthaporn S, Eremin O (2001) Dendritic cells, I: biological functions. J R Coll Surg Edinb 46(1):9PubMed Satthaporn S, Eremin O (2001) Dendritic cells, I: biological functions. J R Coll Surg Edinb 46(1):9PubMed
44.
go back to reference Schwaab T, Schned AR, Heaney JA et al (1999) In vivo description of dendritic cells in human renal cell carcinoma [see comments]. J Urol 162(2):567PubMed Schwaab T, Schned AR, Heaney JA et al (1999) In vivo description of dendritic cells in human renal cell carcinoma [see comments]. J Urol 162(2):567PubMed
45.
go back to reference Snijders A, Kalinski P, Hilkens CM, Kapsenberg ML (1998) High-level IL-12 production by human dendritic cells requires two signals. Int Immunol 10(11):1593CrossRefPubMed Snijders A, Kalinski P, Hilkens CM, Kapsenberg ML (1998) High-level IL-12 production by human dendritic cells requires two signals. Int Immunol 10(11):1593CrossRefPubMed
46.
go back to reference Sogn GA (1998) Tumour immunology: the glass is half full. Immunity 9:757PubMed Sogn GA (1998) Tumour immunology: the glass is half full. Immunity 9:757PubMed
47.
go back to reference Steinman R, Cohn Z (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. J Exp Med 137:1142PubMed Steinman R, Cohn Z (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. J Exp Med 137:1142PubMed
48.
go back to reference Takahashi K, Asagoe K, Zaishun J et al (1998) Heterogeneity of dendritic cells in human superficial lymph node: in vitro maturation of immature dendritic cells into mature or activated interdigitating reticulum cells. Am J Pathol 153(3):745PubMed Takahashi K, Asagoe K, Zaishun J et al (1998) Heterogeneity of dendritic cells in human superficial lymph node: in vitro maturation of immature dendritic cells into mature or activated interdigitating reticulum cells. Am J Pathol 153(3):745PubMed
49.
go back to reference Thurnher M, Radmayr C, Ramoner R et al (1996) Human renal-cell carcinoma tissue contains dendritic cells. Int J Cancer 68(1):1PubMed Thurnher M, Radmayr C, Ramoner R et al (1996) Human renal-cell carcinoma tissue contains dendritic cells. Int J Cancer 68(1):1PubMed
50.
go back to reference Voorhis WC (1982) Human dendritic cells: enrichment and characterisation from peripheral blood. J Exp Med 155:1172PubMed Voorhis WC (1982) Human dendritic cells: enrichment and characterisation from peripheral blood. J Exp Med 155:1172PubMed
51.
go back to reference Xu H, Friedrichs U, Gieseler RK et al (1992) Human blood dendritic cells exhibit a distinct T-cell-stimulating mechanism and differentiation pattern. Scand J Immunol 36(5):689PubMed Xu H, Friedrichs U, Gieseler RK et al (1992) Human blood dendritic cells exhibit a distinct T-cell-stimulating mechanism and differentiation pattern. Scand J Immunol 36(5):689PubMed
52.
go back to reference Young JW, Steinman RM (1988) Accessory cell requirements for the mixed-leukocyte reaction and polyclonal mitogens, as studied with a new technique for enriching blood dendritic cells. Cell Immunol 111(1):167PubMed Young JW, Steinman RM (1988) Accessory cell requirements for the mixed-leukocyte reaction and polyclonal mitogens, as studied with a new technique for enriching blood dendritic cells. Cell Immunol 111(1):167PubMed
53.
go back to reference Zambruno G, Girolomoni G, Manca V et al (1992) Epidermal Langerhans cells after allogeneic bone marrow transplantation: depletion by chemotherapy conditioning regimen alone. J Cutan Pathol 19(3):187PubMed Zambruno G, Girolomoni G, Manca V et al (1992) Epidermal Langerhans cells after allogeneic bone marrow transplantation: depletion by chemotherapy conditioning regimen alone. J Cutan Pathol 19(3):187PubMed
54.
go back to reference Zou JP, Shimizu J, Ikegame K (1992) Tumor-bearing mice exhibit a progressive increase in tumor antigen-presenting cell function and a reciprocal decrease in tumor antigen-responsive CD4+ T cell activity. J Immunol 148:648PubMed Zou JP, Shimizu J, Ikegame K (1992) Tumor-bearing mice exhibit a progressive increase in tumor antigen-presenting cell function and a reciprocal decrease in tumor antigen-responsive CD4+ T cell activity. J Immunol 148:648PubMed
Metadata
Title
Dendritic cells are dysfunctional in patients with operable breast cancer
Authors
Sukchai Satthaporn
Adrian Robins
Wichai Vassanasiri
Mohamed El-Sheemy
Jibril A Jibril
David Clark
David Valerio
Oleg Eremin
Publication date
01-06-2004
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 6/2004
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-003-0485-5

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