Abstract
A large body of evidence supports the notion that both the adaptive and nonadaptive immune systems play an important role in the control of tumor progression in patients with malignant disease. These findings have provided the rationale for the development of active specific immunotherapy for the treatment of malignant disease. The enthusiastic application of active specific immunotherapy in a large number of patients has conclusively shown that:
-
1.
Several of the immunization strategies used elicit a tumor antigen (TA)-specific immune response.
-
2.
The results of immunomonitoring assays in patients treated with active specific immunotherapy have poor, if any, predictive value of clinical responses.
-
3.
Irrespective of the TA or immunization strategy used, clinical responses have only occasionally been observed.
-
4.
Disease frequently progresses and recurs in spite of induction and/or persistence of TA-specific immune responses.
These disappointing findings are likely to reflect, at least in part, the ability of tumor cells to manipulate the ongoing TA-specific immune response as well as evade immune recognition and destruction, utilizing multiple mechanisms. The latter include tumor cell-induced qualitative and/or quantitative defects in the generation and maintenance of TA-specific immune responses, tumor cell-induced immune suppression, and/or changes in the antigenic profile of tumor cells because of their genetic instability. These topics are reviewed in this chapter, following a brief description of the essential components of a TA-specific immune response. Lastly, potential strategies to counteract tumor immune suppression and immune escape mechanisms are discussed, because these approaches may improve the outcome of immunotherapy in patients with malignant disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Restifo NP, Wunderlich JR. Principles of tumor immunity: biology of cellular immune responses. In: DeVita VT, Hellman S, Rosenderg SA, eds. Biologic Therapy of Cancer. Philadelphia: Lippincott. 1996: 3–21.
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3:991–998.
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol 2004; 22:329–360.
Marchand M, Weynants P, Rankin E, et al. Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE-3. Int J Cancer 1995; 63:883–885.
Jaeger E, Bernhard H, Romero P, et al. Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens. Int J Cancer 1996; 66:162–169.
Pittet MJ, Valmori D, Dunbar PR, et al. High frequencies of naïve Melan-A/MART-1-specific CD8+ T cells in a large proportion of human histocompatibility leukocyte antigen HLA-A2 individuals. J Exp Med 1999; 190:705–715.
Parmiani G, Castelli C, Dalerba P, et al. Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where are we going? J Natl Cancer Inst 2002; 94:805–818.
Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res 2003; 90:127–156.
Ohno S, Suzuki N, Ohno Y, Inagawa H, Soma G, Inoue M. Tumor-associated macrophages: foe or accomplice of tumors? Anticancer Res 2003; 23:4395–4409.
Fojo T, Bates S. Strategies for reversing drug resistance. Oncogene 2003; 22:7512–7523.
Pommier Y, Sordet O, Antony S, Hayward RL, Kohn KW. Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene 2004; 23:2934–2949.
Renkvist N, Castelli C, Robbins PF, Parmiani G. A listing of human tumor antigens recognized by T cells. Cancer Immunol Immunother 2001; 50:3–15.
Trikha M, Yan L, Nakada MT. Monoclonal antibodies as therapeutics in oncology. Curr Opin Biotechnol 2002; 13:609–614.
Panelli MC, Wang E, Monsurro V, et al. Vaccination with T cell-defined antigens. Expert Opin Biol Ther 2004; 4:697–707.
Naftzger C, Takechi Y, Kohda H, Hara I, Vijayasaradhi S, Houghton AN. Immune response to a differentiation antigen induced by altered antigen: a study of tumor rejection and autoimmunity. Proc Natl Acad Sci USA 1996; 93:14,809–14,814.
Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 2002; 3:611–618.
Durrant LG, Spendlove I. Cancer vaccines entering Phase III clinical trials. Expert Opin Emerg Drugs 2003; 8:489–500.
Romero P, Cerottini JC, Speiser DE. Monitoring tumor antigen specific T-cell responses in cancer patients and phase I clinical trials of peptide-based vaccination. Cancer Immunol Immunother 2004; 53:249–255.
Sogn JA. Tumor immunology: the glass is half full. Immunity 1998; 9:757–763.
Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol 2000; 74:181–273.
Ferrone S. Tumour immune escape. Semin Cancer Biol 2002; 12:1–86.
Khong HT, Restifo NP. Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat Immunol 2002; 3:999–1005.
Whiteside TL. Apoptosis of immune cells in the tumor microenvironment and peripheral circulation of patients with cancer: implications for immunotherapy. Vaccine 2002; 20(Suppl 4):46–51.
Reilly RT, Machiels JP, Emens LA, et al. The collaboration of both humoral and cellular HER-2/neutargeted immune responses is required for the complete eradication of HER-2/neu-expressing tumors. Cancer Res 2001; 61:880–883.
DiFronzo LA, Gupta RK, Essner R, et al. Enhanced humoral immune response correlates with improved disease-free and overall survival in American Joint Committee on Cancer stage II melanoma patients receiving adjuvant polyvalent vaccine. J Clin Oncol 2002; 20:3242–3248.
Chung MH, Gupta RK, Hsueh E, et al. Humoral immune response to a therapeutic polyvalent cancer vaccine after complete resection of thick primary melanoma and sentinel lymphadenectomy. J Clin Oncol 2003; 21:313–319.
Noorchashm H, Greeley SA, Naji A. The role of t/b lymphocyte collaboration in the regulation of autoimmune and alloimmune responses. Immunol Res 2003; 27:443–450.
DiCarlo E, Forni G, Musiani P. Neutrophils in the antitumoral immune response. Chem Immunol Allergy 2003; 83:182–203.
Yewdell J. Generating peptide ligands for MHC class I molecules. Mol Immunol 2002; 39:125–259.
Velders MP, Markiewicz MA, Eiben GL, Kast WM. CD4+ T cell matters in tumor immunity. Int Rev Immunol 2003; 22:113–140.
Heath WR, Carbone FR. Cross-presentation, dendritic cells, tolerance and immunity. Annu Rev Immunol 2001; 19:47–64.
Li Z, Menoret A, Srivastava P. Roles of heat-shock proteins in antigen presentation and cross-presentation. Curr Opin Immunol 2002; 14:45–51.
Thery C, Amigorena S. The cell biology of antigen presentation in dendritic cells. Curr Opin Immunol 2001; 13:45–51.
Gretz JE, Anderson AO, Shaw S. Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol Rev 1997; 156:11–24.
Cooper MA, Fehniger TA, Fuchs A, Colonna M, Caligiuri MA. NK cell and DC interactions. Trends Immunol 2004; 25:47–52.
Foti M, Granucci F, Ricciardi-Castagnoli P. A central role for tissue-resident dendritic cells in innate responses. Trends Immunol 2004; 25:650–654.
Ikeda H, Chamoto K, Tsuji T, et al. The critical role of type-1 innate and acquired immunity in tumor immunotherapy. Cancer Sci 2004; 95:697–703.
Raulet DH. Interplay of natural killer cells and their receptors with the adaptive immune response. Nat Immunol 2004; 5:996–1002.
Jego G, Pascual V, Palucka AK, Banchereau J. Dendritic cells control B cell growth and differentiation. Curr Dir Autoimmun 2005; 8:124–139.
Allison JP, Hurwitz AA, Leach DR. Manipulation of costimulatory signals to enhance anti-tumor T cell responses. Curr Opin Immunol 1995; 7:682–686.
Barry M, Bleackley RC. Cytotoxic T lymphocytes: all roads lead to death. Nat Rev Immunol 2002; 2:401–409.
Creusot RJ, Mitchison NA. How DCs control cross-regulation between lymphocytes. Trends Immunol 2004; 25:126–131.
Heath WR, Belz GT, Behrens GM, et al. Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev 2004; 199:9–26.
Pulendran B. Modulating TH1/TH2 responses with microbes, dendritic cells, and pathogen recognition receptors. Immunol Res 2004; 29:187–196.
Mazzoni A, Segal DM. Controlling the Toll road to dendritic cell polarization. J Leukoc Biol 2004; 75:721–730.
Reichert TE, Rabinowich H, Johnson JT, Whiteside TL. Human immune cells in the tumor microenvironment: mechanisms responsible for signaling and functional defects. J Immunother 1998; 21:295–306.
Hoffmann TK, Dworacki G, Tsukihiro T, et al. Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance. Clin Cancer Res 2002; 8:2553–2562.
Saito T, Dworacki G, Gooding W, Lotze MT, Whiteside TL. Spontaneous apoptosis of CD8+ T lymphocytes in peripheral blood of patients with advanced melanoma. Clin Cancer Res 2000; 6:1351–1364.
Whiteside TL. Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunol Immunother 1999; 48:346–352.
Whiteside TL. Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol Immunother 2004; 53:865–878.
Kuss I, Saito T, Johnson JT, Whiteside TL. Clinical significance of decreased zeta chain expression in peripheral blood lymphocytes of patients with head and neck cancer. Clin Cancer Res 1999; 5:329–334.
Kurt RA, Urba WJ, Smith JW, Schoof DD. Peripheral T lymphocytes from women with breast cancer exhibit abnormal protein expression of several signaling molecules. Int J Cancer 1998; 78:16–20.
Nakagomi H, Petersson M, Magnusson I, et al. Decreased expression of the signal-transducing ζ chains in tumor-infiltrating T-cell and NK cells of patients with colorectal carcinoma. Cancer Res 1993; 53:5610–5612.
Matsuda M, Petersson M, Lenkei R, et al. Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. Int J Cancer 1995; 61:765–772.
Finke JH, Zea AH, Stanley J, et al. Loss of T-cell receptor ζ chain and p56lck in T-cell infiltrating human renal cell carcinoma. Cancer Res 1993; 53:5613–5616.
Li X, Liu J, Park J-K, Hamilton TA, et al. T cells from renal cell carcinoma patients exhibit an abnormal pattern of NFκB specific DNA binding activity. Cancer Res 1 1994; 54:5424–5429.
Lai P, Rabinowich H, Crowley-Nowick PA, Bell MC, Mantovani G, Whiteside TL. Alterations in expression and function of signal transduction proteins in tumor associated NK and T lymphocytes from patients with ovarian carcinoma. Clin Cancer Res 1996; 2:161–173.
Wang Q, Stanley J, Kudoh S, et al. T cells infiltrating non-Hodgkin’s B cell lymphomas show altered tyrosine phosphorylation pattern even though T cell receptor/CD3-associated kinases are present. J Immunol 1995; 155:1382–1392.
Zea AH, Cutri BD, Longo DL, et al. Alterations in T cell receptor and signal transduction molecules in melanoma patients. Clin Cancer Res 1995; 1:1327–1335.
Kersh EN, Shaw AS, Allen PM. Fidelity of T cell activation through multistep T cell receptor zeta phosphorylation. Science 1998; 281:572–575.
Bukowski RM, Rayman P, Uzzo R, et al. Signal transduction abnormalities in T lymphocytes from patients with advanced renal cell carcinoma: clinical relevance and effects of cytokine therapy. Clin Cancer Res 1998; 4:2337–2347.
Uzzo R, Rayman P, Kolenko V, et al. Renal cell carcinoma-derived gangliosides suppress nuclear factor-κB activation in T cells. J Clin Invest 1999; 104:769–776.
Reichert TE, Strauss L, Wagner EM, Gooding W, Whiteside TL. Signaling abnormalities and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin Cancer Res 2002; 8:3137–3145.
Bauernhofer T, Kuss I, Henderson B, Baum AS, Whiteside TL. Preferential apoptosis of CD56dim natural killer cell subset in patients with cancer. Eur J Immunol 2003; 33:119–124.
Kolenko V, Wang Q, Riedy MC, et al. Tumor-induced suppression of T lymphocyte proliferation coincides with inhibition of Jak3 expression and IL-2 receptor signaling: role of soluble products from human renal cell carcinomas. J Immunol 1997; 159:3057–3067.
Uzzo RG, Clark PE, Rayman P, et al. Evidence that tumor inhibits NFκB activation in T lymphocytes of patients with renal cell carcinoma. J Natl Cancer Inst 1999; 91:718–721.
Reichert TE, Day R, Wagner E, Whiteside TL. Absent or low expression of the ζ chain in T cells at the tumor site correlates with poor survival in patients with oral carcinoma. Cancer Res 1998; 58:5344–5347.
Kono K, Ressing ME, Brandt RM, et al. Decreased expression of signal-transducing zeta chain in peripheral T cells and natural killer cells in patients with cervical cancer. Clin Cancer Res 1996; 2:1825–1828.
de Gruijl TD, Bontkes HJ, Peccatori F, et al. Expression of CD3-zeta on T-cells in primary cervical carcinoma and in metastasis-positive and-negative pelvic lymph nodes. Br J Cancer 1999; 79:1127–1132.
Yang L, Carbone DP. Tumor-host immune interactions and dendritic cell dysfunction. Adv Cancer Res 2004; 92:13–27.
Mantovani A, Allavena P, Sozzani S, Vecchi A, Locati M, Sica A. Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin Cancer Biol 2004; 14:155–160.
Mantovani A, Bottazzi B, Colotta F, Sozzani S, Ruco L. The origin and function of tumor-associated macrophages. Immunol Today 1992; 13:265–270.
Whiteside TL, Rabinowich H. The role of Fas/FasL in immunosuppression induced by human tumors. Cancer Immunol Immunother 1998; 46:175–184.
Andreola G, Rivoltini L, Castelli C, et al. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med 2002; 195:1303–1316.
Abrahams VM, Straszewski SL, Kamsteeg M, et al. Epithelial ovarian cancer cells secrete Fas ligand. Cancer Res 2003; 63:5573–5581.
Taylor DD, Gercel-Taylor C, Lyons KS, Stanson J, Whiteside TL. T-cell apoptosis and suppression of T-cell receptor/CD3-ζ by Fas ligand-containing membrane vesicles shed from ovarian tumors. Clin Cancer Res 2003; 9:5113–5119.
Shurin MR, Lu L, Kalinski P, Stewart-Akers AM, Lotze MT. Th1/Th2 balance in cancer, transplantation and pregnancy. Springer Semin Immunopathol 1999; 21:339–359.
Rivoltini L, Carrabba M, Huber V, et al. Immunity to cancer: attack and escape in T lymphocyte-tumor cell interaction. Immunol Rev 2002; 188:97–113.
Singh RK, Varney ML. IL-8 expression in malignant melanoma: implications in growth and metastasis. Histol Histopathol 2000; 15:843–849.
Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 2002; 419:734–738.
Doubrovina ES, Doubrovin MM, Vider E, et al. Evasion from NK cell immunity by MHC class I chainrelated molecules expressing colon adenocarcinoma. J Immunol 2003; 171:6891–6899.
Wu JD, Higgins LM, Steinle A, Cosman D, Haugk K, Plymate SR. Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer. J Clin Invest 2004; 114:560–568.
Streit M, Detmar M. Angiogenesis, lymphangiogenesis, and melanoma metastasis. Oncogene 2003; 22:3172–3179.
Finke J, Ferrone S, Frey A, Mufson A, Ochoa A. Where have all the T cells gone? Mechanisms of immune evasion by tumors. Immunol Today 1999; 20:158–160.
Ivanov VN, Bhoumik A, Ronai Z. Death receptors and melanoma resistance to apoptosis. Oncogene 2003; 22:3152–3161.
Van Parijs L, Ibrahimov A, Abbas AK. The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity 1996; 93:951–955.
Carreno BM, Collins M. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Annu Rev Immunol 2002; 20:29–53.
Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 2004; 4:336–347.
Shurin MR, Gabrilovich DI. Regulation of dendritic cell system by tumor. Cancer Res Ther Control 2001; 11:65–78.
Pirtskhalaishvili G, Shurin GV, Esche C, Salup RR, Lotze MT, Shurin MR. Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins. Br J Cancer 2000; 83:506–513.
Esche C, Shurin GV, Kirkwood JM, et al. TNF-α-promoted expression of Bcl-2 and inhibition of mitochondrial cytochrome c release mediated resistance of mature dendritic cells to melanoma-induced apoptosis. Clin Cancer Res 2001; 7:974–979.
Moretta L, Ferlazzo G, Mingari MC, Melioli G, Moretta A. Human natural killer cell function and their interactions with dendritic cells. Vaccine 2003; 21(Suppl 2):S38–S42.
Gabrilovich DI, Velders MP, Sotomayor EM, Kast WM. Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. J Immunol 2001; 166:5398–5406.
Terabe M, Matsui S, Park JM, et al. Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J Exp Med 2003; 198:1741–1752.
Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI. Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 2004; 172:989–999.
Serafini P, De Santo C, Marigo I, et al. Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 2004; 53:64–72.
Terabe M, Berzofsky JA. Immunoregulatory T cells in tumor immunity. Curr Opin Immunol 2004; 16:157–162.
Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 2002; 169:2756–2761.
Woo EY, Chu CS, Goletz TJ, et al. Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 2001; 61:4766–4772.
Onyango P. Genomics and cancer. Curr Opin Oncol 2002; 14:79–85.
Riker A, Cormier J, Panelli M, et al. Immune selection after antigen-specific immunotherapy of melanoma. Surgery 1999; 126:112–120.
Hoffmann TK, Nakano K, Elder EM, et al. Generation of T cells specific for the wild-type sequence p53(264–272) peptide in cancer patients: implications for immunoselection of epitope loss variants. J Immunol 2000; 165:5938–5944.
Slingluff CL Jr, Colella TA, Thompson L, et al. Melanomas with concordant loss of multiple melanocytic differentiation proteins: immune escape that may be overcome by targeting unique or undefined antigens. Cancer Immunol Immunother 2000; 48:661–672.
Saleh FH, Crotty KA, Hersey P, Menzies SW, Rahman W. Autonomous histopathological regression of primary tumours associated with specific immune responses to cancer antigens. J Pathol 2003; 200:383–395.
Chang CC, Campoli M, Ferrone S. HLA class I antigens and malignant disease. Adv Cancer Res 2005; 93:189–234.
Landowski TH, Qu N, Buyuksal I, Painter JS, Dalton WS. Mutations in the Fas antigen in patients with multiple myeloma. Blood 1997; 90:4266–4270.
Shin MS, Park WS, Kim SY, et al. Alterations of Fas (Apo-1/CD95) gene in cutaneous malignant melanoma. Am J Pathol 1999; 154:1785–1791.
Medema JP, de Jong J, Peltenburg LT, et al. Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc Natl Acad Sci USA 2001; 98:11,515–11,520.
Trapani JA, Sutton VR, Smyth MJ. CTL granules: evolution of vesicles essential for combating virus infections. Immunol Today 1999; 20:351–356.
Mailliard RB, Egawa S, Cai Q, et al. Complementary dendritic cell-activating function of CD8+ and CD4+ cells: helper role of CD8+ T cells in the development of T helper type 1 responses. J Exp Med 2002; 195:473–483.
Mailliard RB, Son Y-I, Redlinger R, et al. Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell helper function. J Immunol 2003; 171:2366–2373.
Tatsumi T, Kierstead LS, Ranieri E, et al. MAGE-6 encodes DRβ1*0401-presented epitopes recognized by CD4+ T cells derived from patients with melanoma or renal cell carcinoma. Clin Cancer Res 2003; 9:947–954.
Lotze MT. Cytokines and the treatment of cancer. In: Weir DM, Herzenberg LA, Herzenberg LA, Blackwell CC, eds. The Handbook of Experimental Immunology, 5th Edition. Cambridge, MA: Blackwell Sciences. 1996: pp. 199.1–199.25.
Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 2001; 19:565–594.
Phan GQ, Yang JC, Sherry RM, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 2003; 100:8372–8377.
Yu Z, Restifo NP. Cancer vaccines: progress reveals new complexities. J Clin Invest 2002; 110:289–294.
Bystryn JC, Zeleniuch-Jacquotte A, Oratz R, Shapiro RL, Harris MN, Roses DF. Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine. Clin Cancer Res 2001; 7:1882–1887.
Belli F, Testori A, Rivoltini L, et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J Clin Oncol 2002; 20:4169–4180.
Berd D. M-Vax: an autologous, hapten-modified vaccine for human cancer. Expert Opin Biol Ther 2002; 2:335–342.
Ward S, Casey D, Labarthe MC, et al. Immunotherapeutic potential of whole tumour cells. Cancer Immunol Immunother 2002; 51:351–357.
Rivoltini L, Castelli C, Carrabba M, et al. Human tumor-derived heat shock protein 96 mediates in vitro activation and in vivo expansion of melanoma-and colon carcinoma-specific T cells. J Immunol 2003; 171:3467–3474.
Kiessling R, Wasserman K, Horiguchi S, et al. Tumor-induced immune dysfunction. Cancer Immunol Immunother 1999; 48:353–362.
Pawelec G, Heinzel S, Kiessling R, Muller L, Ouyang Q, Zeuthen J. Escape mechanisms in tumor immunity: a year 2000 update. Crit Rev Oncog 2000; 11:97–133.
Morton DL, Hsueh EC, Essner R, et al. Prolonged survival of patients receiving active immunotherapy with Canvaxin therapeutic polyvalent vaccine after complete resection of melanoma metastatic to regional lymph nodes. Ann Surg 2002; 236:438–448.
Sosman JA, Unger JM, Liu PY, et al. Adjuvant immunotherapy of resected, intermediate-thickness, node-negative melanoma with an allogeneic tumor vaccine: impact of HLA class I antigen expression on outcome. J Clin Oncol 2002; 20:2067–2075.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
Campoli, M., Ferrone, S. (2006). Tumor-Induced Immune Suppression and Immune Escape. In: Disis, M.L. (eds) Immunotherapy of Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59745-011-1:263
Download citation
DOI: https://doi.org/10.1385/1-59745-011-1:263
Publisher Name: Humana Press
Print ISBN: 978-1-58829-564-4
Online ISBN: 978-1-59745-011-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)