Modulating T-cell immunity to tumours: new strategies for monitoring T-cell responses (original) (raw)
van den Eynde, B. J. & van der Bruggen, P. T cell defined tumor antigens. Curr. Opin. Immunol.9, 684–693 (1997). CASPubMed Google Scholar
Mitchell, M. S. Perspective on allogeneic melanoma lysates in active specific immunotherapy. Semin. Oncol.25, 623–635 (1998). CASPubMed Google Scholar
Hsueh, E. C. et al. Active specific immunotherapy with polyvalent melanoma cell vaccine for patients with in-transit melanoma metastases. Cancer85, 2160–2169 (1999). CASPubMed Google Scholar
Musselli, C., Livingston, P. O. & Ragupathi, G. Keyhole limpet hemocyanin conjugate vaccines against cancer: the Memorial Sloan–Kettering experience. J. Cancer Res. Clin. Oncol.127 (Suppl. 2), R20–R26 (2001). CASPubMed Google Scholar
Dranoff, G. et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte–macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc. Natl Acad. Sci. USA90, 3539–3543 (1993). CASPubMedPubMed Central Google Scholar
Sampson, J. H. et al. Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the 'immunologically privileged' central nervous system. Proc. Natl Acad. Sci. USA93, 10399–10404 (1996). CASPubMedPubMed Central Google Scholar
Simons, J. W. et al. Bioactivity of autologous irradiated renal cell carcinoma vaccines generated by ex vivo granulocyte–macrophage colony-stimulating factor gene transfer. Cancer Res.57, 1537–1546 (1997). CASPubMedPubMed Central Google Scholar
Tuting, T. et al. Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the TH1-biasing cytokines IL-12 and IFN-α. J. Immunol.160, 1139–1147 (1998). CASPubMed Google Scholar
Kwak, L. W. et al. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N. Engl. J. Med.327, 1209–1215 (1992). CASPubMed Google Scholar
Boczkowski, D., Nair, S. K., Snyder, D. & Gilboa, E. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J. Exp. Med.184, 465–472 (1996). CASPubMed Google Scholar
Larregina, A. T. et al. Direct transfection and activation of human cutaneous dendritic cells. Gene Ther.8, 608–617 (2001). CASPubMed Google Scholar
Reichardt, V. L. et al. Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma: a feasibility study. Blood93, 2411–2419 (1999). CASPubMed Google Scholar
Reddy, S. A., Okada, C., Wong, C., Bahler, D. & Levy, R. T cell antigen receptor vaccines for active therapy of T cell malignancies. Ann. NY Acad. Sci.941, 97–105 (2001). CASPubMed Google Scholar
Nestle, F. O. et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nature Med.4, 328–332 (1998). CASPubMed Google Scholar
Fong, L. et al. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc. Natl Acad. Sci. USA98, 8809–8814 (2001).In a clinical trial using dendritic cells pulsed with an altered peptide ligand of CEA to vaccinate patients with colon cancer, the authors show, using tetramer analysis, that expansion of CEA-specific T cellsin vivocorrelated with clinical responses. CASPubMedPubMed Central Google Scholar
Thurner, B. et al. Vaccination with Mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J. Exp. Med.190, 1669–1678 (1999).Regression of individual lesions were observed in 6 out of 11 patients with advanced melanoma receiving a MAGE3-pulsed dendritic-cell vaccine. Antigen-loss variants were identified in residual tumour of some patients. CASPubMedPubMed Central Google Scholar
Rosenberg, S. A., Spiess, P. & Lafreniere, R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science233, 1318–1321 (1986). CASPubMed Google Scholar
Riddell, S. R. et al. Phase I study of cellular adoptive immunotherapy using genetically modified CD8+ HIV-specific T cells for HIV seropositive patients undergoing allogeneic bone marrow transplant. The Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine, Department of Medicine, Division of Oncology. Hum. Gene Ther.3, 319–338 (1992). CASPubMed Google Scholar
Yee, C. et al. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of T cell-mediated vitiligo. J. Exp. Med.192, 1637–1644 (2000).In a patient receiving adoptive therapy with T-cell clones targeting MART1, transferred T cells were tracked with peptide–MHC tetramers and shown to migrate to antigen-positive sites of skin and tumour and to mediate an antigen-specific immune response. CASPubMedPubMed Central Google Scholar
Yee, C., Riddell, S. R. & Greenberg, P. D. Prospects for adoptive T cell therapy. Curr. Opin. Immunol.9, 702–708 (1997). CASPubMed Google Scholar
Yee, C., Savage, P. A., Lee, P. P., Davis, M. M. & Greenberg, P. D. Isolation of high avidity melanoma-reactive CTL from heterogeneous populations using peptide–MHC tetramers. J. Immunol.162, 2227–2234 (1999).Peptide–MHC tetramers were used to define the TCR affinity of antigen-specific T cells (see also reference87). CASPubMed Google Scholar
Simon, R. M. et al. Clinical trial designs for the early clinical development of therapeutic cancer vaccines. J. Clin. Oncol.19, 1848–1854 (2001). CASPubMed Google Scholar
Disis, M. L. et al. Delayed-type hypersensitivity response is a predictor of peripheral blood T-cell immunity after HER-2/neu peptide immunization. Clin. Cancer Res.6, 1347–1350 (2000). CASPubMed Google Scholar
Habal, N. et al. CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer. Ann. Surg. Oncol.8, 389–401 (2001). CASPubMed Google Scholar
Hsueh, E. C., Gupta, R. K., Qi, K. & Morton, D. L. Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine. J. Clin. Oncol.16, 2913–2920 (1998). CASPubMed Google Scholar
Lee, P. et al. Effects of interleukin-12 on the immune response to a multipeptide vaccine for resected metastatic melanoma. J. Clin. Oncol.19, 3836–3847 (2001). CASPubMed Google Scholar
Hsu, F. J. et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med.2, 52–58 (1996). CASPubMed Google Scholar
Bendandi, M. et al. Complete molecular remissions induced by patient-specific vaccination plus granulocyte–monocyte colony-stimulating factor against lymphoma. Nature Med.5, 1171–1177 (1999). CASPubMed Google Scholar
Marchand, M. et al. Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE3. Int. J. Cancer63, 883–885 (1995). CASPubMed Google Scholar
Marchand, M. et al. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int. J. Cancer80, 219–230 (1999). CASPubMed Google Scholar
Mukherji, B. et al. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc. Natl Acad. Sci. USA92, 8078–8082 (1995). CASPubMedPubMed Central Google Scholar
Cormier, J. N. et al. Enhancement of cellular immunity in melanoma patients immunized with a peptide from Mart1/Melan A. Cancer J. Sci. Am.3, 37–44 (1997). CASPubMedPubMed Central Google Scholar
Rosenberg, S. A. et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nature Med.4, 321–327 (1998). CASPubMed Google Scholar
Jager, E. et al. Monitoring CD8 T cell responses to NY-ESO-1: correlation of humoral and cellular immune responses. Proc. Natl Acad. Sci. USA97, 4760–4765 (2000).References26–34describe some of the clinical trials that involve augmentation of an antigen-specific T-cell response. CASPubMedPubMed Central Google Scholar
Altman, J. D. et al. Phenotypic analysis of antigen-specific T lymphocytes. Science274, 94–96 (1996). CASPubMed Google Scholar
Davis, M. M. et al. T cell receptor biochemistry, repertoire selection and general features of TCR and Ig structure. Ciba Found. Symp.204, 94–100; discussion 100–104 (1997). CASPubMed Google Scholar
Schneck, J. P. Monitoring antigen-specific T cells using MHC–Ig dimers. Immunol. Invest.29, 163–169 (2000). CASPubMed Google Scholar
Yee, C., Davis, M. M. & Lee, P. P. The Use of Peptide–MHC Tetramers in T-Cell Therapy of Melanoma (Academic Press, San Diego, 2000). Google Scholar
Lee, P. P. et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nature Med.5, 677–685 (1999).Multiparametric analysis of endogenous populations of circulating tumour-specific T cells revealed an activational defect in T cells that recognize melanoma-associated differentiation antigens. CASPubMed Google Scholar
Callan, M. F. et al. Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein–Barr virus in vivo. J. Exp. Med.187, 1395–1402 (1998). CASPubMedPubMed Central Google Scholar
Haanen, J. et al. In situ detection of virus- and tumor-specific T-cell immunity. Nature Med.6, 1056–1060 (2000). CASPubMed Google Scholar
Lee, K. H. et al. Functional dissociation between local and systemic immune response during anti-melanoma peptide vaccination. J. Immunol.161, 4183–4194 (1998). CASPubMed Google Scholar
Pongers-Willemse, M. J. et al. Real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia using junctional region specific TaqMan probes. Leukemia12, 2006–2014 (1998). CASPubMed Google Scholar
Coulie, P. G. et al. A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. Proc. Natl Acad. Sci. USA98, 10290–10295 (2001). CASPubMedPubMed Central Google Scholar
Riddell, S. R. et al. T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nature Med.2, 216–223 (1996). CASPubMed Google Scholar
Thomis, D. C. et al. A FAS-based suicide switch in human T cells for the treatment of graft-versus-host disease. Blood97, 1249–1257 (2001). CASPubMed Google Scholar
Brodie, S. J. et al. In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nature Med.5, 34–41 (1999).In situlocalization of gene-marked T-cell clonesin situfollowing adoptive T-cell therapy. CASPubMed Google Scholar
Lamana, M. L., Segovia, J. C., Guenechea, G. & Bueren, J. A. Systematic analysis of clinically applicable conditions leading to a high efficiency of transduction and transgene expression in human T cells. J. Gene Med.3, 32–41 (2001). CASPubMed Google Scholar
Kammula, U. S. et al. Functional analysis of antigen-specific T lymphocytes by serial measurement of gene expression in peripheral blood mononuclear cells and tumor specimens. J. Immunol.163, 6867–6875 (1999).Application of real-time PCR analysis of cytokine expression to evaluate antigen-specific T-cell response to vaccination. CASPubMed Google Scholar
Mocellin, S., Ohnmacht, G. A., Wang, E. & Marincola, F. M. Kinetics of cytokine expression in melanoma metastases classifies immune responsiveness. Int. J. Cancer93, 236–242 (2001). CASPubMed Google Scholar
Pala, P., Hussell, T. & Openshaw, P. J. M. Flow cytometric measurement of intracellular cytokines. J. Immunol. Methods243, 107–124 (2000). CASPubMed Google Scholar
Murali-Krishna, K. et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity8, 177–187 (1998). CASPubMed Google Scholar
Becker, C. et al. Adoptive tumor therapy with T lymphocytes enriched through an IFN-γ capture assay. Nature Med.7, 1159–1162 (2001). CASPubMed Google Scholar
Herr, W., Schneider, J., Lohse, A. W., Meyer zum Buschenfelde, K. H. & Wolfel, T. Detection and quantification of blood-derived CD8+ T lymphocytes secreting tumor necrosis factor-α in response to HLA-A2.1-binding melanoma and viral peptide antigens. J. Immunol. Methods191, 131–142 (1996). CASPubMed Google Scholar
Gnjatic, S. et al. Strategy for monitoring T cell responses to NY-ESO-1 in patients with any HLA class I allele. Proc. Natl Acad. Sci. USA97, 10917–10922 (2000). CASPubMedPubMed Central Google Scholar
Herr, W. et al. The use of computer-assisted video image analysis for the quantification of CD8+ T lymphocytes producing tumor necrosis factor-α spots in response to peptide antigens. J. Immunol. Methods203, 141–152 (1997). CASPubMed Google Scholar
Zajac, A. J. et al. Viral immune evasion due to persistence of activated T cells without effector function. J. Exp. Med.188, 2205–2213 (1998). CASPubMedPubMed Central Google Scholar
Taswell, C. Limiting dilution assays for the determination of immunocompetent cell frequencies. III. Validity tests for the single-hit Poisson model. J. Immunol. Methods72, 29–40 (1984). CASPubMed Google Scholar
Jager, E. et al. Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers. Proc. Natl Acad. Sci. USA97, 12198–12203 (2000).Stabilization and regression of individual metastases in some patients with melanoma, receiving a peptide vaccine that targets NY-ESO-1, provide evidence of clinical correlation with ELISPOT analyses. CASPubMedPubMed Central Google Scholar
Molldrem, J. J. et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nature Med.6, 1018–1023 (2000). CASPubMed Google Scholar
Lee, K. H. et al. Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression. J. Immunol.163, 6292–6300 (1999). CASPubMed Google Scholar
Fong, L. et al. Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy. J. Immunol.167, 7150–7156 (2001). CASPubMed Google Scholar
Cheever, M. A., Thompson, D. B., Klarnet, J. P. & Greenberg, P. D. Antigen-driven long term-cultured T cells proliferate in vivo, distribute widely, mediate specific tumor therapy, and persist long-term as functional memory T cells. J. Exp. Med.163, 1100–1112 (1986). CASPubMed Google Scholar
Ohlen, C., Kalos, M., Hong, D. J., Shur, A. C. & Greenberg, P. D. Expression of a tolerizing tumor antigen in peripheral tissue does not preclude recovery of high-affinity CD8+ T cells or CTL immunotherapy of tumors expressing the antigen. J. Immunol.166, 2863–2870 (2001). CASPubMed Google Scholar
Ochsenbein, A. F. et al. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc. Natl Acad. Sci. USA96, 2233–2238 (1999). CASPubMedPubMed Central Google Scholar
Mihm, M. C. Jr, Clemente, C. G. & Cascinelli, N. Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response. Lab. Invest.74, 43–47 (1996). PubMed Google Scholar
Underwood, J. C. Lymphoreticular infiltration in human tumours: prognostic and biological implications: a review. Br. J. Cancer30, 538–548 (1974). CASPubMedPubMed Central Google Scholar
Watt, A. G. & House, A. K. Colonic carcinoma: a quantitative assessment of lymphocyte infiltration at the periphery of colonic tumors related to prognosis. Cancer41, 279–282 (1978). CASPubMed Google Scholar
van Nagell, J. R. Jr, Donaldson, E. S., Wood, E. G. & Parker, J. C. Jr. The significance of vascular invasion and lymphocytic infiltration in invasive cervical cancer. Cancer41, 228–234 (1978). PubMed Google Scholar
Hanson, H. L. et al. Eradication of established tumors by CD8+ T cell adoptive immunotherapy. Immunity13, 265–276 (2000). CASPubMed Google Scholar
Speiser, D. E. & Ohashi, P. S. Activation of cytotoxic T cells by solid tumours? Cell. Mol. Life Sci.54, 263–271 (1998). CASPubMed Google Scholar
Ochsenbein, A. F. et al. Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature411, 1058–1064 (2001). CASPubMed Google Scholar
Hardy, J. et al. Bioluminescence imaging of lymphocyte trafficking in vivo. Exp. Hematol.29, 1353–1360 (2001). CASPubMed Google Scholar
Mizoguchi, H. et al. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science258, 1795–1798 (1992). CASPubMed Google Scholar
Correa, M. R. et al. Sequential development of structural and functional alterations in T cells from tumor-bearing mice. J. Immunol.158, 5292–5296 (1997). CASPubMed Google Scholar
Moser, J. M., Gibbs, J., Jensen, P. E. & Lukacher, A. E. CD94-NKG2A receptors regulate antiviral CD8+ T cell responses. Nature Immunol.3, 189–195 (2002). CAS Google Scholar
Deeths, M. J., Kedl, R. M. & Mescher, M. F. CD8+ T cells become nonresponsive (anergic) following activation in the presence of costimulation. J. Immunol.163, 102–110 (1999). CASPubMed Google Scholar
Staveley-O'Carroll, K. et al. Induction of antigen-specific T cell anergy: an early event in the course of tumor progression. Proc. Natl Acad. Sci. USA95, 1178–1183 (1998). CASPubMedPubMed Central Google Scholar
Torre-Amione, G. et al. A highly immunogenic tumor transfected with a murine transforming growth factor type-β1 cDNA escapes immune surveillance. Proc. Natl Acad. Sci. USA87, 1486–1490 (1990). CASPubMedPubMed Central Google Scholar
Novak, E. J., Liu, A. W., Nepom, G. T. & Kwok, W. W. MHC class II tetramers identify peptide-specific human CD4+ T cells proliferating in response to influenza A antigen. J. Clin. Invest.104, R63–R67 (1999).Authors develop peptide–MHC class II tetramers that recognize human antigen-specific CD4+ T cells.
Toes, R. E., Offringa, R., Blom, R. J., Melief, C. J. & Kast, W. M. Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction. Proc. Natl Acad. Sci. USA93, 7855–7860 (1996). CASPubMedPubMed Central Google Scholar
Alexander-Miller, M. A., Leggatt, G. R. & Berzofsky, J. A. Selective expansion of high- or low-avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. Proc. Natl Acad. Sci. USA93, 4102–4107 (1996). CASPubMedPubMed Central Google Scholar
Gervois, N., Guilloux, Y., Diez, E. & Jotereau, F. Suboptimal activation of melanoma infiltrating lymphocytes (TIL) due to low avidity of TCR/MHC–tumor peptide interactions. J. Exp. Med.183, 2403–2407 (1996). CASPubMed Google Scholar
Crawford, F., Kozono, H., White, J., Marrack, P. & Kappler, J. Detection of antigen-specific T cells with multivalent soluble class II MHC covalent peptide complexes. Immunity8, 675–682 (1998). CASPubMed Google Scholar
Savage, P. A., Boniface, J. J. & Davis, M. M. A kinetic basis for T cell receptor repertoire selection during an immune response. Immunity10, 485–492 (1999). CASPubMed Google Scholar
Noppen, C., Spagnoli, G. C. & Schaefer, C. Isolation of multiple mRNAs from a few eukaryotic cells: a fast method to obtain templates for RT-PCR. Biotechniques21, 394–396 (1996). CASPubMed Google Scholar
Dutoit, V. et al. Functional avidity of tumor antigen-specific CTL recognition directly correlates with the stability of MHC/peptide multimer binding to TCR. J. Immunol.168, 1167–1171 (2002).Peptide–MHC tetramers were used to define the TCR affinity of antigen-specific T cells (see also reference21). CASPubMed Google Scholar
Kessels, H. W., Wolkers, M. C., van den Boom, M. D., van der Valk, M. A. & Schumacher, T. N. Immunotherapy through TCR gene transfer. Nature Immunol.2, 957–961 (2001).Designing T cells with a given antigen specificity by the transfer of genes that encode the TCR. CAS Google Scholar
Urban, J. L., Holland, J. M., Kripke, M. L. & Schreider, H. Immunoselection of tumor cell variants by mice suppressed with ultraviolet radiation. J. Exp. Med.156, 1025–1041 (1982). CASPubMed Google Scholar
Saleh, F. H., Crotty, K. A., Hersey, P. & Menzies, S. W. Primary melanoma tumour regression associated with an immune response to the tumour-associated antigen Melan-A/ MART-1. Int. J. Cancer94, 551–557 (2001). CASPubMed Google Scholar
Shankaran, V. et al. IFN-γ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature410, 1107–1111 (2001).Endogenous immunoselection of tumour cells can lead to the appearance of antigen-loss tumour variants that escape immune detection in the immunocompetent host. CASPubMed Google Scholar
Panelli, M. C. et al. Expansion of tumor–T cell pairs from fine needle aspirates of melanoma metastases. J. Immunol.164, 495–504 (2000). CASPubMed Google Scholar
Vitale, M. et al. HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. Cancer Res.58, 737–742 (1998). CASPubMed Google Scholar
Ferrone, S. & Marincola, F. M. Loss of HLA class I antigens by melanoma cells: molecular mechanisms, functional significance and clinical relevance. Immunol. Today16, 487–494 (1995). CASPubMed Google Scholar
Hicklin, D. J., Kageshita, T. & Ferrone, S. Development and characterization of rabbit antisera to human MHC-linked transporters associated with antigen processing. Tissue Antigens48, 38–46 (1996). CASPubMed Google Scholar
Wang, Z., Margulies, L., Hicklin, D. J. & Ferrone, S. Molecular and functional phenotypes of melanoma cells with abnormalities in HLA class I antigen expression. Tissue Antigens47, 382–390 (1996). CASPubMed Google Scholar
Yang, G., Hellstrom, K. E., Mizuno, M. T. & Chen, L. In vitro priming of tumor-reactive cytolytic T lymphocytes by combining IL-10 with B7–CD28 costimulation. J. Immunol.155, 3897–3903 (1995). CASPubMed Google Scholar
Beck, C., Schreiber, H. & Rowley, D. Role of TGF-β in immune-evasion of cancer. Microsc. Res. Tech.52, 387–395 (2001). CASPubMed Google Scholar
Barth, R. J. Jr, Camp, B. J., Martuscello, T. A., Dain, B. J. & Memoli, V.A. The cytokine microenvironment of human colon carcinoma. Lymphocyte expression of tumor necrosis factor-α and interleukin-4 predicts improved survival. Cancer78, 1168–1178 (1996). PubMed Google Scholar
Zea, A. H. et al. Alterations in T cell receptor and signal transduction molecules in melanoma patients. Clin. Cancer Res.1, 1327–1335 (1995). CASPubMed Google Scholar
Maccalli, C. et al. Differential loss of T cell signaling molecules in metastatic melanoma patients' T lymphocyte subsets expressing distinct TCR variable regions. J. Immunol.163, 6912–6923 (1999). CASPubMed Google Scholar
Bladergroen, B. A. et al. Expression of the granzyme B inhibitor, protease inhibitor 9, by tumor cells in patients with non-Hodgkin and Hodgkin lymphoma: a novel protective mechanism for tumor cells to circumvent the immune system? Blood99, 232–237 (2002). CASPubMed Google Scholar
Medema, J. P., de Jong, J., van Hall, T., Melief, C. J. & Offringa, R. Immune escape of tumors in vivo by expression of cellular FLICE-inhibitory protein. J. Exp. Med.190, 1033–1038 (1999). CASPubMedPubMed Central Google Scholar
Ambrosini, G., Adida, C. & Altieri, D.C. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nature Med.3, 917–921 (1997). CASPubMed Google Scholar
Nakashima, M., Sonoda, K. & Watanabe, T. Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1. Nature Med.5, 938–942 (1999). CASPubMed Google Scholar
Mellado, M., de Ana, A. M., Moreno, M. C., Martinez, C. & Rodriguez-Frade, J. M. A potential immune escape mechanism by melanoma cells through the activation of chemokine-induced T cell death. Curr. Biol.11, 691–696 (2001). CASPubMed Google Scholar
Riker, A. I. et al. Development and characterization of melanoma cell lines established by fine-needle aspiration biopsy: advances in the monitoring of patients with metastatic melanoma. Cancer Detect. Prev.23, 387–396 (1999).References93–107describe mechanisms of tumour immune escape through defects in antigen expression or antigen presentation (references93–96), the presence of an immune-suppressive tumour microenvironment (references97–101) and tumour upregulation of immunoprotective mechanisms (references101–107). CASPubMed Google Scholar