Top

Published in:

01-10-2004 | Review

Escape from immunotherapy: possible mechanisms that influence tumor regression/progression

Authors: Murrium Ahmad, Robert C. Rees, Selman A. Ali

Published in: Cancer Immunology, Immunotherapy | Issue 10/2004

Abstract

Tumor escape is one major obstacle that has to be addressed prior to designing and delivering successful immunotherapy. There is compelling evidence to support the notion that immunogenic tumors, in murine models and cancer patients, can be rejected by the immune system under optimum conditions for activating adaptive and nonadaptive antitumor immune responses. Despite this capability, a large number of tumors continue to grow and evade recognition and/or destruction by the immune system. The limited success in current immunotherapeutic strategies may be due to a variety of reasons: failure of effector cells to compete with the growing tumor burden, production of humoral factors by tumors that locally block cytotoxicity, antigen/MHC loss, T-cell dysfunction, production of suppressor T cells—to name but a few causes for therapeutic ineffectiveness for the particular malignancy being treated. To optimize immunotherapy strategies, correction of immune-activating signals, eradication of inhibitory factors, and the evasion from newly developed immunoresistant tumor phenotypes need to be simultaneously considered.

Jakobisiak M, Lasek W, Golab J (2003) Natural mechanisms protecting against cancer. Immunol Lett 90(2–3):103–22

Speiser DE, Rimoldi D, Batard P, Lienard D, Lejeune F, Cerottini JC, Romero P (2003) Disease-driven T cell activation predicts immune responses to vaccination against melanoma. Cancer Immunol 3:12

Romero P (2003) IL-31 Monitoring natural and vaccine induced T cell responses in melanoma. Pigment Cell Res 16(5):588CrossRef

Jager E, Jager D, Knuth A (2000) CTL-defined cancer vaccines in melanoma and other epithelial cancer. In: Stern PL, Beverely PCL, Carroll MW (eds) Cancer vaccines and immunotherapy. Cambridge University Press, Cambridge, pp 207

Kaufmann HL, Schlorn J (2000) Vaccines in colon cancer. In: Stern PL, Beverely PCL, Carroll MW (eds) Cancer Vaccines and Immunotherapy. Cambridge University Press, Cambridge, p 107

Rudolf MP, Small LA, Velders MP, DaSilva DM, Weijzens S, Kast MW (2000) Vaccine delivery and immunosuppression in cervical cancer. In: Stern PL, Beverely PCL, Carroll MW (eds) Cancer vaccines and immunotherapy. Cambridge University Press, Cambridge, p 82

Taylor Papadimitriou J, Burchell J, Miles DW (2000) MUC1 vaccines and breast cancer. In: Cancer vaccines and immunotherapy. Stern PL, Beverely PCL, Carroll MW (eds) Cambridge University Press, Cambridge, p 135

Stevenson FK, Zhu D, Spellerberg, M, King CA, Sahota SS, Rice J, Thompsett AR, Hamblin TJ (2000) DNA vaccines against B-cell tumors. In: Stern PL, Beverely PCL, Carroll MW (eds) Cancer vaccines and immunotherapy. Cambridge University Press, Cambridge, p 218

Adams M, Jasani B, Colaco CS, Mason MD (2000) Dendritic cell approaches to immunotherapy. In: Stern PL, Beverely PCL, Carroll MW (eds) Cancer vaccines and immunotherapy. Cambridge University Press, Cambridge, p 237

10.

Ciavarra RP, Brown RR, Holterman DA, Garrett M, Glass WF 2nd, Wright GL Jr, Schellhammer PF, Somers KD (2003) Impact of the tumor microenvironment on host infiltrating cells and the efficacy of flt3-ligand combination immunotherapy evaluated in a treatment model of mouse prostate cancer. Cancer Immunol Immunother 52(9):535–545CrossRefPubMed

11.

Cabrera T, Lopez-Nevot MA, Gaforio JJ, Ruiz-Cabello F, Garrido F (2003) Analysis of HLA expression in human tumor tissues. Cancer Immunol Immunother. 52:1–9

12.

Clark RE, Dodi IA, Hill SC, Lill JR, Aubert G, Macintyre AR, Rojas J, Bourdon A, Bonner PL, Wang L, Christmas SE, Travers PJ, Creaser CS, Rees RC, Madrigal JA (2001) Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein. Blood 98(10):2887–2893CrossRefPubMed

13.

Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3(11):991–998CrossRefPubMed

14.

Pardoll D (2001) T cells and tumors. Nature 411(12):1010–1012CrossRef

15.

Khong HT, Restifo NP (2002) Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat Immunol 3(11):999–1005CrossRefPubMed

16.

Muller L, Kiessling R, Rees RC, Pawelec G (2002) Escape mechanisms in tumor immunity: an update. J Environ Pathol Toxicol Oncol 21(4):277–330PubMed

17.

Rivoltini L, Carrabba M, Huber V, Castelli C, Novellino L, Dalerba P, Mortarini R, Arancia G, Anichini A, Fais S, Parmiani G (2002) Immunity to cancer: attack and escape in T lymphocyte-tumor cell interaction. Immunol Rev 188:97–113CrossRefPubMed

18.

Pardoll DM (1998) Cancer vaccines. Nat Med 5[Suppl 4]:525–531

19.

Melcher A, Todryk S, Hardwick N, Ford M, Jacobson M, Vile RG (1998) Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med (5):581–587

20.

Ali SA, McLean CS, Boursnell ME, Martin G, Holmes CL, Reeder S, Entwisle C, Blakeley DM, Shields JG, Todryk S, Vile R, Robins RA, Rees RC (2000) Preclinical evaluation of “whole” cell vaccines for prophylaxis and therapy using a disabled infectious single cycle-herpes simplex virus vector to transduce cytokine genes. Cancer Res 60(6):1663–1670PubMed

21.

Kovacsovics-Bankowski M, Rock KL (1995) A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules. Science 267(5195):243–246PubMed

22.

Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12:991–1045PubMed

23.

Algarra I, Collado A, Garrido F (1997) Altered MHC class I antigens in tumors. Int J Clin Lab Res 27(2):95–102PubMed

24.

Johnsen AK, France J, Nagy N, Askew D, Abdul-Karim FW, Gerson SL, Sy MS, Harding CV (2001) Systemic deficits in transporter for antigen presentation (TAP)-1 or proteasome subunit LMP2 have little or no effect on tumor incidence. Int J Cancer 91(3):366–372CrossRefPubMed

25.

Restifo NP (1996) The new vaccines: building viruses that elicit antitumor immunity. Curr Opin Immunol 8(5):658–663CrossRefPubMed

26.

Zheng P, Sarma S, Guo Y, Liu Y (1999) Two mechanisms for tumor evasion of preexisting cytotoxic T-cell responses: lessons from recurrent tumors. Cancer Res 59(14):3461–3467PubMed

27.

de Vries TJ, Fourkour A, Wobbes T, Verkroost G, Ruiter DJ, van Muijen GN (1997) Heterogeneous expression of immunotherapy candidate proteins gp100, MART-1, and tyrosinase in human melanoma cell lines and in human melanocytic lesions. Cancer Res 57(15):3223–3229PubMed

28.

Hofbauer GF, Kamarashev J, Geertsen R, Boni R, Dummer R (1998) Melan A/MART-1 immunoreactivity in formalin-fixed paraffin-embedded primary and metastatic melanoma: frequency and distribution. Melanoma Res 8(4):337–343PubMed

29.

Davidson WF, Giese T, Fredrickson TN (1998) Spontaneous development of plasmacytoid tumors in mice with defective Fas-Fas ligand interactions. Exp Med 187(11):1825–38PubMed

30.

Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J (1997) Inhibition of death receptor signals by cellular FLIP. Nature 388(6638):190–195

31.

Medema JP, de Jong J, van Hall T, Melief CJ, Offringa R (1999) Immune escape of tumors in vivo by expression of cellular FLICE-inhibitory protein. J Exp Med 190(7):1033–1038CrossRefPubMed

32.

Takeda K, Smyth MJ, Cretney E, Hayakawa Y, Yamaguchi N, Yagita H, Okumura K (2001) Involvement of tumor necrosis factor-related apoptosis-inducing ligand in NK cell-mediated and IFN-gamma-dependent suppression of subcutaneous tumor growth. Cell Immunol 214(2):194–200CrossRefPubMed

33.

Taylor MW, Feng GS (1991) Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J 5(11):2516–2522PubMed

34.

Schwartz RH (1990) A cell culture model for T lymphocyte clonal anergy. Science 248(4961):1349–1356PubMed

35.

Oyama T, Ran S, Ishida T, Nadaf S, Kerr L, Carbone DP, Gabrilovich DI (1998) VEGF affects DC maturation through the inhibition of NF-kB activation in haemopoietic cells. J Immunol 160(3):1224–1232PubMed

36.

Bronte V, Apolloni E, Cabrelle A, Ronca R, Serafini P, Zamboni P, Restifo NP, Zanovello P (2000) Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells Blood 96(12):3838–3846

37.

Gabrilovich DI, Velders MP, Sotomayor EM, Kast WM (2001) Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. J Immunol 166(9):5398–406PubMed

38.

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

39.

McHugh RS, Whitters MJ, Piccirillo CA, Young DA, Shevach EM, Collins M, Byrne MC (2002) CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 16(2):311–323PubMed

40.

Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP, Toes RE, Offringa R, Melief CJ (2001) Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med 194(6):823–832PubMed

41.

Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB (2002) Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med 196(4):459–468CrossRefPubMed

42.

Mellor AL, Munn DH (1999) Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 20(10):469–473CrossRefPubMed

43.

Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van Den Eynde BJ (2003) Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9(10):1269–1274CrossRefPubMed

44.

Swanson KA, Zheng Y, Heidler KM, Mizobuchi T, Wilkes DS (2004) CD11c+ cells modulate pulmonary immune responses by production of indoleamine 2,3-dioxygenase. Am J Respir Cell Mol Biol 30(3):311–318CrossRefPubMed

45.

Ahmad M, Rees RC, McArdle SEB, Li G, Mian S, Entwisle C, Loudon P, Ali SA (2003) Regulation of CTL responses to a MHC- restricted class I peptide of the gp70 tumor antigen by splenic parenchymal CD4⁺ T cells in mice failing immunotherapy with DISC-mGM-CSF (Submitted)

46.

Takeda K, Smyth MJ, Cretney E, Hayakawa Y, Kayagaki N, Yagita H, Okumura K (2002) Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. J Exp Med 195(2):161–169CrossRefPubMed

47.

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):1867–1870CrossRefPubMed

48.

Koopman LA, Corver WE, van der Slik AR, Giphart MJ, Fleuren GJ (2000) Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class I loss in cervical cancer. J Exp Med 191:961–975PubMed

49.

Hicklin DJ, Francesco M, Marincola FM, Ferrone S (1999) HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story. Mol Med Today 5:178– 186PubMed

50.

Garrido F, Algarra I (2001) MHC antigens and tumor escape from immune surveillance. Adv Cancer Res 83:117–158PubMed

51.

Keating PJ, Cromme FV, Duggan-Keen M, Snijders PJ, Walboomers JM, Hunter RD, Dyer PA, Stern PL (1995) Frequency of downregulation of individual HLA-A and –B alleles in cervical carcinomas in relation to TAP-1 expression. Br J Cancer 72(2):405–411PubMed

52.

Perez B, Benitez R, Fernandez MA, Oliva MR, Soto JL, Serrano S, Lopez Nevot MA, Garrido F (1999) A new beta 2 microglobulin mutation found in a melanoma tumor cell line. Tissue Antigens 53(6):569–572PubMed

53.

Serrano A, Tanzarella S, Lionello I, Mendez R, Traversari C, Ruiz-Cabello F, Garrido F (2001) Rexpression of HLA class I antigens and restoration of antigen-specific CTL response in melanoma cells following 5-aza-2’-deoxycytidine treatment. Int J Cancer 94(2):243–251CrossRefPubMed

54.

Feenstra M, Verdaasdonk M, van der Zwan AW, de Weger R, Slootweg P, Tilanus M (2000) Microsatellite analysis of microdissected tumor cells and 6p high density microsatellite analysis in head and neck squamous cell carcinomas with down-regulated human leukocyte antigen class I expression. Lab Invest 80(3):405–414PubMed

55.

Ramal LM, Feenstra M, van der Zwan AW, Collado A, Lopez-Nevot MA, Tilanus M, Garrido F (2000) Criteria to define HLA haplotype loss in human solid tumors. Tissue Antigens 55(5):443–448PubMed

56.

Ramal LM, Maleno I, Cabrera T, Collado A, Ferron A, Lopez-Nevot MA, Garrido F (2000) Molecular strategies to define HLA haplotype loss in microdissected tumor cells. Hum Immunol 61(10):1001–1012PubMed

57.

Browning MJ, Krausa P, Rowan A, Hill AB, Bicknell DC, Bodmer JG, Bodmer WF (1993) Loss of human leukocyte antigen expression on colorectal tumor cell lines: implications for anti-tumor immunity and immunotherapy. J Immunother 14(3):163–168PubMed

58.

Griffioen M, Ouwerkerk IJ, Harten V, Schrier PI (2000) HLA-B locus-specific downregulation in human melanoma requires enhancer A as well as a sequence element located downstream of the transcription initiation site. Immunogenetics 52(1–2):121–128

59.

Soong TW, Hui KM (1991) Regulation of the expression of major histocompatibility complex class I genes in human colorectal cancer. Cancer Detect Prev 15(3):231–239PubMed

60.

Ikeda H, Lethe B, Lehmann F, van Baren N, Baurain JF, de Smet C, Chambost H, Vitale M, Moretta A, Boon T, Coulie PG (1997) Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 6(2):199–208PubMed

61.

Real LM, Jimenez P, Kirkin A, Serrano A, Garcia A, Canton J, Zeuthen J, Garrido F, Ruiz-Cabello F (2001) Multiple mechanisms of immune evasion can coexist in melanoma tumor cell lines derived from the same patient. Cancer Immunol Immunother (11):621–628CrossRef

62.

Cabrera T, Pedrajas G, Cozar JM, Garrido A, Vincente J, Tallada M, Garrido F (2003) HLA class I expression in bladder carcinomas. Tissue Antigens 62(4):324–327CrossRefPubMed

63.

Cabrera T, Maleno I, Lopez-Nevot MA, Redondo M, Fernandez MA, Collado A, Garrido F (2003) High frequency of HLA- B44 allelic loss in human solid tumors. Hum Immunol 64(10):941–950CrossRefPubMed

64.

Cabrera CM, Jimenez P, Cabrera T, Esparza C, Ruiz-Cabello F, Garrido F (2003) Total loss of MHC class I in colorectal tumors can be explained by two molecular pathways: beta 2-microglobulin inactivation and MSI-positive tumors and LMP7/TAP2 downregulation in MS negative tumors. Tissue Antigens 61(3):211–219PubMed

65.

Ali SA, Lynam J, McLean CS, Entwisle C, Loudon P, Rojas JM, McArdle SE, Li G, Mian S, Rees RC (2002) Tumor regression induced by intratumor therapy with a disabled infectious single cycle (DISC) herpes simplex virus (HSV) vector, DISC/HSV/murine granulocyte-macrophage colony-stimulating factor, correlates with antigen-specific adaptive immunity. J Immunol 168(7):3512–3519PubMed

66.

Boursnell MEG, Entwistle C, Ali SA, Sivasubramaniam SD, Reeder SP, McLean CS, Blakeley DM, Miller J, Hill S, Shields, JG, Inglis SC, Rees RC (1998) Disabled infectious single cycle (DISC) herpes simplex virus as a vector for immunotherapy of cancer. Adv Exp Med Biol 451:379–384PubMed

67.

Rees RC, McArdle S, Mian S, Li G, Ahmad M, Parkinson R, Ali SA (2002) Disabled Infectious single cycle-herpes simplex virus (DISC-HSV) as a vector for immunogene therapy of cancer. Curr Opin Mol Ther 4:49–53PubMed

68.

Todryk S, Ali SA, Dalgleish A, Rees RC (2001) Genetically modified tumor cells for cancer immunisation. In: Robins RA, Rees RC (eds) Cancer immunology. Kluwer, The Netherlands, pp 181–194

69.

Restifo NP, Marincola FM, Kawakami Y, Taubenberger J, Yannelli JR, Rosenberg SA (1996) Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J Natl Cancer Inst 88(2):100–108PubMed

70.

Ugurel S, Uhlig D, Pfohler C, Tilgen W, Schadendorf D, Reinhold U (2004) Down-regulation of HLA class II and co-stimulatory CD86/B7.2 on circulating monocytes from melanoma patients. Cancer Immunol Immunother 53(6):551–559CrossRefPubMed

71.

Le YS, Kim TE, Kim BK, Park YG, Kim GM, Jee SB, Ryu KS, Kim IK, Kim JW (2002) Alterations of HLA class I and class II antigen expression in borderline invasive and metastatic ovarian cancers. Exp Mol Med 34(1):18–26PubMed

72.

Maiorana A, Cesinaro AM, Fano RA, Collina G (1995) Expression of MHC class I and class II antigens in primary breast carcinomas and synchronous nodal metastases. Clin Exp Metastasis 13(1):43–48PubMed

73.

Sharpe JC, Abel PD, Gilbertson JA, Brawn P, Foster CS (1994) Modulated expression of human leucocyte antigen class I and class II determinants in hyperplastic and malignant human prostatic epithelium. Br J Urol 74(5):609–616PubMed

74.

Uyttenhove C, Godfraind C, Lethe B, Amar-Costesec A, Renauld JC, Gajewski TF, Duffour MT, Warnier G, Boon T, Van den Eynde BJ (1997) The expression of mouse gene P1A in testis does not prevent safe induction of cytolytic T cells against a P1A-encoded tumor antigen. Int J Cancer 70(3):349–356CrossRefPubMed

75.

Ciurea A, Hunziker L, Martinic MM, Oxenius A, Hengartner H, Zinkernagel RM (2001) CD4+ T-cell-epitope escape mutant virus selected in vivo. Nat Med 7:795–800CrossRefPubMed

76.

Rohrlich PS, Cardinaud S, Firat H, Lamari M, Briand P, Escriou N, Lemonnier FA (2003) HLA-B*0702 transgenic, H-2KbDb double-knockout mice: phenotypical and functional characterization in response to influenza virus. Int Immunol 15:765–772CrossRefPubMed

77.

Bai XF, Liu J, Li O, Zheng P, Liu Y (2003) Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes. J Clin Invest 111(10):1487–1496CrossRefPubMed

78.

Lozupone F, Rivoltini L, Luciani F, Venditti M, Lugini L, Cova A, Squarcina P, Parmiani G, Belardelli F, Fais S (2003) Adoptive transfer of an anti-MART-1(27–35)-specific CD8+ T cell clone leads to immunoselection of human melanoma antigen-loss variants in SCID mice. Eur J Immunol 33(2):556–566CrossRefPubMed

79.

Maeurer MJ, Gollin SM, Martin D, Swaney W, Bryant J, Castelli C, Robbins P, Parmiani G, Storkus WJ, Lotze MT (1996) Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen. J Clin Invest 98(7):1633–1641PubMed

80.

Chen YL, Chen SH, Wang JY, Yang BC (2003) Fas ligand on tumor cells mediates inactivation of neutrophils. J Immunol 171(3):1183–1191PubMed

81.

Ragnarsson GB, Mikaelsdottir EK, Vidarsson H, Jonasson JG, Olafsdottir K, Kristjansdottir K, Kjartansson J, Ogmundsdottir HM, Rafnar T (2000) Intracellular Fas ligand in normal and malignant breast epithelium does not induce apoptosis in Fas-sensitive cells. Br J Cancer 83(12):1715–1721CrossRefPubMed

82.

Osaki M, Kase S, Adachi K, Takeda A, Hashimoto K, Ito H (2004) Inhibition of the PI3 K-Akt signaling pathway enhances the sensitivity of Fas-mediated apoptosis in human gastric carcinoma cell line, MKN-45. J Cancer Res Clin Oncol 130(1):8–14 CrossRefPubMed

83.

Fennell DA (2003) Bcl-2 as a target for overcoming chemoresistance in small-cell lung cancer. Clin Lung Cancer 4(5):307–313PubMed

84.

Salvesen GS, Dixit VM (1999) Caspase activation: the induced-proximity model. Proc Natl Acad Sci U S A 96(20):10964–10967CrossRefPubMed

85.

Groneberg C, Pickartz T, Binder A, Ringel F, Srock S, Sieber T, Schoeler D, Schriever F (2003) Clinical relevance of CD95 (Fas/Apo-1) on T cells of patients with B-cell chronic lymphocytic leukemia. Exp Hematol 31(8):682–685CrossRefPubMed

86.

Hersey P, Zhang XD (2001) How melanoma cells evade trail-induced apoptosis. Nat Rev Cancer 1(2):142–150CrossRefPubMed

87.

Kase H, Aoki Y, Tanaka K (2003) Fas ligand expression in cervical adenocarcinoma: relevance to lymph node metastasis and tumor progression. Gynecol Oncol 90(1):70–74CrossRefPubMed

88.

Song E, Chen J, Ouyang N, Su F, Wang M, Heemann U (2001) Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte apoptosis: an active mode of immune evasion in colon cancer. Br J Cancer 85(7):1047–1054CrossRefPubMed

89.

Li R, Ruttinger D, Li R, Si LS, Wang YL (2003) Analysis of the immunological microenvironment at the tumor site in patients with non-small cell lung cancer. Langenbecks Arch Surg 388(6):406–412CrossRefPubMed

90.

Toi M, Taniguchi T, Yamamoto Y, Kurisaki T, Suzuki H, Tominaga T (1996) Clinical significance of the determination of angiogenic factors. Eur J Cancer 32A(14):2513–2529PubMed

91.

Ohm JE, Carbone DP (2001) VEGF as a mediator of tumor associated immunodeficiency. Immunol Res 23(2–3):263–272

92.

Lissoni P, Malugani F, Bonfanti A, Bucovec R, Secondino S, Brivio F, Ferrari–Bravo A, Ferrante R, Vigore L, Rovelli F, Mandala M, Vivian Fumagalli L, Gardani GS (2001) Abnormally enhanced blood concentrations of VEGF in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1. J Biol Regul Homeost Agents 15(2):140–144

93.

Inoshima N, Nakanishi Y, Minami T, Izumi M, Takayama K, Yoshin Hara N (2002) The influence of dendritic cell infilteration and VEGF expression on the prognosis of NSCLC. Clin Cancer Res 8(11):3480–3486

94.

Fan XH, Han BH, Dong QG, Sha HF, Bao GL, Liao ML (2003) Vascular endothelial growth factor inhibits dendritic cells from patients with NSCLC. Zhonghua Jie He He Xi Za Zhi (9):539 – 543

95.

Buggins AG, Milojkovic D, Arno MJ, Lea NC, Mufti GJ, Thomas NS, Hirst WJ (2001) Microenvironment produced by acute myeloid leukemia cells prevents T cell activation and proliferation by inhibition of NF-kappaB, c-Myc, and pRb pathways. J Immunol 167(10):6021–6030PubMed

96.

Fortis C, Foppoli M, Gianotti L, Galli L, Citterio G, Consogno G, Gentilini O, Braga M (1996) Increased interleukin-10 serum levels in patients with solid tumors. Cancer Lett 104(1):1–5CrossRefPubMed

97.

Bellone G, Turletti A, Artusio E, Mareschi K, Carbone A, Tibaudi D, Robecchi A, Emanuelli G, Rodeck U (1999) Tumor-associated transforming growth factor-beta and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients. Am J Pathol 155(2):537–547PubMed

98.

Mukherjee P, Ginardi AR, Madsen CS, Tinder TL, Jacobs F, Parker J, Agrawal B, Longenecker BM, Gendler SJ (2001) MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment. Glycoconj J 18(11–12):931–942

99.

De Smedt T, Van Mechelen M, De Becker G, Urbain J, Leo O, Moser M (1997) Effect of interleukin-10 on dendritic cell maturation and function. Eur J Immunol 27(5):1229–1235PubMed

100.

Sharma S, Stolina M, Lin Y, Gardner B, Miller PW, Kronenberg M, Dubinett SM (1999) T cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function. J Immunol 163(9):5020–5028PubMed

101.

Tsushima H, Kawata S, Tamura S, Ito N, Shirai Y, Kiso S, Imai Y, Shimomukai H, Nomura Y, Matsuda Y, Matsuzawa Y (1996) High levels of transforming growth factor beta 1 in patients with colorectal cancer: association with disease progression. Gastroenterology 110(2):375–382PubMed

102.

Gorsch SM, Memoli VA, Stukel TA, Gold LI, Arrick BA (1992) Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. Cancer Res 52(24):6949–6952PubMed

103.

Doran T, Stuhlmiller H, Kim JA, Martin EW Jr, Triozzi PL (1997) Oncogene and cytokine expression of human colorectal tumors responding to immunotherapy. J Immunother 20(5):372–376PubMed

104.

Krasagakis K, Tholke D, Farthmann B, Eberle J, Mansmann U, Orfanos CE (1998) Elevated plasma levels of transforming growth factor (TGF)-beta1 and TGF-beta2 in patients with disseminated malignant melanoma. Br J Cancer 77(9):1492–1494PubMed

105.

Maeda H, Shiraishi A (1996) TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice. J Immunol 156(1):73–78PubMed

106.

von Bernstorff W, Voss M, Freichel S, Schmid A, Vogel I, Johnk C, Henne-Bruns D, Kremer B, Kalthoff H (2001) Systemic and local immunosuppression in pancreatic cancer patients. Clin Cancer Res 7[Suppl 3]:925s–932sPubMed

107.

Janeway CA, Travers P, Walport M, Shlomchik M (2002) Immunobiology: the immune system in health and disease, 5th edn. Garland, New York

108.

Nieland JD, Loviscek K, Kono K, Albain KS, McCall AR, Potkul RK, Fisher SG, Velders MP, Petersson M, Kiessling R, Kast WM (1998) PBLs of early breast carcinoma patients with a high nuclear grade tumor unlike PBLs of cervical carcinoma patients do not show a decreased TCR zeta expression but are functionally impaired. J Immunother 21(4):317–322PubMed

109.

Kono K, Salazar-Onfray F, Petersson M, Hansson J, Masucci G, Wasserman K, Nakazawa T, Anderson P, Kiessling R (1996) Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell-and natural killer cell-mediated cytotoxicity. Eur J Immunol 26(6):1308–1313PubMed

110.

Nakagomi H, Petersson M, Magnusson I, Juhlin C, Matsuda M, Mellstedt H, Taupin JL, Vivier E, Anderson P, Kiessling R (1993) Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma. Cancer Res 53(23):5610–5612PubMed

111.

Schule J, Bergkvist L, Hakansson L, Gustafsson B, Hakansson A (2002) Down-regulation of the CD3-zeta chain in sentinel node biopsies from breast cancer patients. Breast Cancer Res Treat 74(1):33–40CrossRefPubMed

112.

Gruss HJ, Dower SK (1995) Tumor necrosis factor ligand superfamily: involvement in the pathology of malignant lymphomas. Blood 85:3378–404PubMed

113.

Smith CA, Farrah T, Goodwin RG (1994) The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76:959–962PubMed

114.

Abken H, Hombach A, Heuser C, Kronfeld K, Seliger B (2002) Tuning tumor-specific T-cell activation: a matter of costimulation? Trends Immunol 23(5):240–245CrossRefPubMed

115.

Chen L, McGowan P, Ashe S, Johnston J, Li Y, Hellstrom I, Hellstrom KE (1994) Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity. J Exp Med 179(2):523–532PubMed

116.

Gaken J, Jiang J, Daniel K, van Berkel E, Hughes C, Kuiper M, Darling D, Tavassoli M, Galea-Lauri J, Ford K, Kemeny M, Russell S, Farzaneh F (2000) Fusagene vectors: a novel strategy for the expression of multiple genes from a single cistron. Gene Ther 7(23):1979–1985CrossRefPubMed

117.

Wen XY, Mandelbaum S, Li ZH, Hitt M, Graham FL, Hawley RG, Stewart AK (2001) Tricistronic viral vectors co-expressing interleukin 12 (IL-12) and CD80 (B7.1) for the immunotherapy of cancer: preclinical studies in myeloma. Cancer Gene Ther 8(5):361–370CrossRefPubMed

118.

Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellstrom KE, Mittler RS, Chen L (1997) Monoclonal antibodies against the 4–1BB T-cell activation molecule eradicate established tumors. Nat Med 3(6):682–685PubMed

119.

Wilcox RA, Flies DB, Zhu G, Johnson AJ, Tamada K, Chapoval AI, Strome SE, Pease LR, Chen L (2002) Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J Clin Invest 109(5):651–659CrossRefPubMed

120.

Weinberg AD, Rivera MM, Prell R, Morris A, Ramstad T, Vetto JT, Urba WJ, Alvord G, Bunce C, Shields J (2000) Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J Immunol 164(4):2160–2169PubMed

121.

Levey DL, Srivastava PK (1996) Alterations in T cells of cancer-bearers: whence specificity? Immunol Today 17:365–368CrossRefPubMed

122.

Plescia OJ, Grinwich K, Plescia AM (1976) Subversive activity of syngeneic tumor cells as an escape mechanism from immune surveillance and the role of prostaglandins. Ann N Y Acad Sci 276:455–465PubMed

123.

Dye ES, North RJ (1981) T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases. J Exp Med 154(4):1033–1042PubMed

124.

Thornton AM, Shevach EM (2000) Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol 164:183–190PubMed

125.

Antony PA, Restifo NP (2002) Do CD4+ CD25+ immunoregulatory T cells hinder tumor immunotherapy? J Immunother 25(3):202–206CrossRefPubMed

126.

Javia LR, Rosenberg SA (2003) CD4+CD25+ suppressor lymphocytes in the circulation of patients immunized against melanoma antigens. J Immunother 26:85–93CrossRefPubMed

127.

Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A (2003) CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer 98:1089–1099CrossRefPubMed

128.

Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CH (2001) Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 61(12):4766–4767PubMed

129.

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

130.

Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166(1):678–89PubMed

131.

Otsuji M, Kimura Y, Aoe T, Okamoto Y, Saito T (1996) Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 zeta chain of T-cell receptor complex and antigen-specific T-cell responses. Proc Natl Acad Sci U S A 93(23):13119–13124CrossRefPubMed

Title: Escape from immunotherapy: possible mechanisms that influence tumor regression/progression
Authors: Murrium Ahmad
Robert C. Rees
Selman A. Ali
Publication date: 01-10-2004
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 10/2004
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-004-0540-x

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2004

The paradox of T cell–mediated antitumor immunity in spite of poor clinical outcome in human melanoma

Effective immunotherapy against cancer

Expression of NK-associated receptors on cytotoxic T cells from melanoma patients: a two-edged sword?

Targeting of tumor cells by lymphocytes engineered to express chimeric receptor genes

The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape

Down-regulation of ζ-chain expression in T cells: a biomarker of prognosis in cancer?

Keynote webinar | Spotlight on antibody–drug conjugates in cancer