Concluding Remarks

The Revised Authoritative Guide To Vaccine Legal Exemptions

Vaccines Have Serious Side Effects

Get Instant Access

Owing to the abundant experimental and clinical evidence, there should no longer be any doubt for the existence of cancer immunoediting from immune surveillance to escape. Cancer cells are gradually able to gain several mechanisms of immune evasion during tumor progression even though they are pursued by the initial and continuing phases of immune surveillance. Immuno-logical sculpting contributes to immune selection pressure, which produces tumor cell variants that are resistant to immune effector cells due to their low immunogenic-ity. In advanced cancers, the marked shifting to immunosuppressive conditions due to the constitution of the immunosuppres-sive network in tumors makes it more difficult to provoke an immune activation to eliminate cancer cells. Given that adoptive immunotherapy using the peptide vaccine and DC transfer is not sufficient to reduce tumor volume and tumor elimination by direct priming for T cells in such conditions, indirect cross-priming for T cells, which can be induced by massive cell death in combination with anticancer drugs, will be required. Indeed, the modulation of anticancer drug-induced cell death as well as the activation of antitumor immune responses by using molecular targeting drugs, such as antibodies and small molecules, may provide remarkable enhancement of chemotherapeutic effects in cancer therapy. Further studies on cellular and molecular mechanisms to contribute to antitumor immune responses will be needed.


Asselin-Paturel, C., and Trinchieri, G. (2005). Production of type I interferons: Plasmacytoid dendritic cells and beyond. J. Exp. Med. 202, 461-465.

Birkeland, S. A., Storm, H. H., Lamm, L. U., Barlow, L., Blohme, I., Forsberg, B., Eklund, B., Fjeldborg, O., Friedberg, M., Frodin, L., et al. (1995). Cancer risk after renal transplantation in the Nordic countries, 1964-1986. Int. J. Cancer 60, 183-189.

Burnet, F. M. (1957). Cancer: A biological approach. Br. Med. J. 1, 841-847.

Burnet, F. M. (1971). Immunological surveillance in neoplasia. Transplant Rev. 7, 3-25.

Cankovic, M., Linden, M. D., and Zarbo, R. J. (2006). Use of microsatellite analysis in detection of tumor lineage as a cause of death in a liver transplant patient. Arch. Pathol. Lab. Med. 130, 529-532.

Dighe, A. S., Richards, E., Old, L. J., and Schreiber, R. D. (1994). Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1, 447456.

Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., and Schreiber, R. D. (2002). Cancer immunoediting: From immunosurveillance to tumor escape. Nat. Immunol. 3, 991-998.

Dunn, G. P., Old, L. J., and Schreiber, R. D. (2004). The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21, 137-148.

Dunn, G. P., Bruce, A. T., Sheehan, K. C., Shankaran, V., Uppaluri, R, Bui, J. D., Diamond, M. S., Koebel, C. M., Arthur, C., White, J. M., et al. (2005). A critical function for type I interferons in cancer immunoediting. Nat. Immunol. 6, 722-729.

Ehrlich, P. (1909). Ueber den jetzigen stand der karzinomforschung. Ned. Tijdschr. Geneeskd. 5, 273290.

Engel, A. M., Svane, I. M., Mouritsen, S., Rygaard, J., Clausen, J., and Werdelin, O. (1996). Methylcholan-threne-induced sarcomas in nude mice have short induction times and relatively low levels of surface MHC class I expression. APMIS 104, 629-639.

Engel, A. M., Svane, I. M., Rygaard, J., and Werdelin, O. (1997). MCA sarcomas induced in scid mice are more immunogenic than MCA sarcomas induced in congenic, immunocompetent mice. Scand. J. Immunol. 45, 463-470.

Girardi, M., Oppenheim, D. E., Steele, C. R., Lewis, J. M., Glusac, E., Filler, R., Hobby, P., Sutton, B., Tigelaar, R. E., and Hayday, A. C. (2001). Regulation of cutaneous malignancy by gammadelta T cells. Science 294, 605-609.

Gresser, I., Bandu, M. T., and Brouty-Boye, D. (1974). Interferon and cell division. IX. Interferon-resistant L1210 cells: Characteristics and origin. J. Natl. Cancer Inst. 52, 553-559.

Gresser, I., Maury, C., Vignaux, F., Haller, O., Belar-delli, F., and Tovey, M. G. (1988). Antibody to mouse interferon alpha/beta abrogates resistance to the multiplication of Friend erythroleukemia cells in the livers of allogeneic mice. J. Exp. Med. 168, 12711291.

Haanen, J. B., Baars, A., Gomez, R., Weder, P., Smits, M., de Gruijl, T. D., von Blomberg, B. M., Bloemena, E., Scheper, R. J., van Ham, S. M., et al. (2006). Melanoma-specific tumor-infiltrating lymphocytes but not circulating melanoma-specific T cells may predict survival in resected advanced-stage mela noma patients. Cancer Immunol. Immunother. 55, 451-458.

Hayakawa, Y., Rovero, S., Forni, G., and Smyth, M. J. (2003). Alpha-galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis. Proc. Natl. Acad. Sci. USA 100, 94649469.

Herberman, R. B., and Holden, H. T. (1978). Natural cell-mediated immunity. Adv. Cancer Res. 27, 305377.

Ikehara, S., Pahwa, R. N., Fernandes, G., Hansen, C. T., and Good, R. A. (1984). Functional T cells in athymic nude mice. Proc. Natl. Acad. Sci. USA 81, 886-888.

Ishigami, S., Natsugoe, S., Tokuda, K., Nakajo, A., Che, X., Iwashige, H., Aridome, K., Hokita, S., and Aikou, T. (2000). Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer 88, 577-583.

Kaplan, D. H., Shankaran, V., Dighe, A. S., Stockert, E., Aguet, M., Old, L .J., and Schreiber, R. D. (1998). Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc. Natl. Acad. Sci. USA 95, 7556-7561.

Kim, R., Emi, M., Tanabe, K., and Arihiro, K. (2006). Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res. 66, 5527-5536.

Klein, G. (1976). Immune surveillance—A powerful mechanism with a limited range. Natl. Cancer Inst. Monogr. 44, 109-113.

Kondo, E., Koda, K., Takiguchi, N., Oda, K., Seike, K., Ishizuka, M., and Miyazaki, M. (2003). Preoperative natural killer cell activity as a prognostic factor for distant metastasis following surgery for colon cancer. Dig. Surg. 20, 445-451.

Lockhart, D. C., Chan, A. K., Mak, S., Joo, H. G., Daust, H. A., Carritte, A., Douville, C. C., Goedegebuure, P. S., and Eberlein, T. J. (2001). Loss of T-cell receptor-CD3zeta and T-cell function in tumor-infiltrating lymphocytes but not in tumor-associated lymphocytes in ovarian carcinoma. Surgery 129, 749-756.

MacKie, R. M., Reid, R., and Junor, B. (2003). Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery. N. Engl. J. Med. 348, 567568.

Maleckar, J. R., and Sherman, L. A. (1987). The composition of the T cell receptor repertoire in nude mice. J. Immunol. 138, 3873-3876.

Malmberg, K. J. (2004). Effective immunotherapy against cancer: A question of overcoming immune suppression and immune escape? Cancer Immunol. Immunother. 53, 879-892.

Morath, C., Mueller, M., Goldschmidt, H., Schwenger, V., Opelz, G., and Zeier, M. (2004). Malignancy in renal transplantation. J. Am. Soc. Nephrol. 15, 15821588.

Myron Kauffman, H., McBride, M. A., Cherikh, W. S., Spain, P. C., Marks, W. H., and Roza, A. M. (2002). Transplant tumor registry: Donor related malignancies. Transplantation 74, 358-362.

Naito, Y., Saito, K., Shiiba, K., Ohuchi, A., Saigenji, K., Nagura, H., and Ohtani, H. (1998). CD8 + T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 58, 3491-3494.

Old, L. J., and Boyse, E. A. (1964). Immunology of experimental tumors. Annu. Rev. Med. 15, 167-186.

Pham, S. M., Kormos, R. L., Landreneau, R. J., Kawai,

B. G., and Griffith, B. P. (1995). Solid tumors after heart transplantation: Lethality of lung cancer. Ann. Thorac. Surg. 60, 1623-1626.

Prehn, R. T., and Main, J. M. (1957). Immunity to meth-ylcholanthrene-induced sarcomas. J. Natl. Cancer Inst. 18, 769-778.

Reichert, T. E., Day, R., Wagner, E. M., and Whiteside, T. L. (1998). Absent or low expression of the zeta chain in T cells at the tumor site correlates with poor survival in patients with oral carcinoma. Cancer Res. 58, 5344-5347.

Riccobon, A., Gunelli, R., Ridolfi, R., De Paola, F., Flamini, E., Fiori, M., Saltutti, C., Petrini, M., Fiammenghi, L., Stefanelli, M., et al. (2004). Im-munosuppression in renal cancer: Differential expression of signal transduction molecules in tumor-infiltrating, near-tumor tissue, and peripheral blood lymphocytes. Cancer Invest. 22, 871-877.

Rosenberg, S. A., Yang, J. C., and Restifo, N. P. (2004). Cancer immunotherapy: Moving beyond current vaccines. Nat. Med. 10, 909-915.

Russell, J. H., and Ley, T. J. (2002). Lymphocyte-mediated cytotoxicity. Annu. Rev. Immunol. 20, 323370.

Rygaard, J., and Povlsen, C. O. (1974). The mouse mutant nude does not develop spontaneous tumours. An argument against immunological surveillance. Acta. Pathol. Microbiol. Scand. Microbiol. Immunol. 82, 99-106.

Sato, E., Olson, S. H., Ahn, J., Bundy, B., Nishikawa, H., Qian, F., Jungbluth, A. A., Frosina, D., Gnjatic, S., Ambrosone, C., et al. (2005). Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/ regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc. Natl. Acad. Sci. USA 102, 18538-18543.

Schmielau, J., Nalesnik, M. A., and Finn, O. J. (2001). Suppressed T-cell receptor zeta chain expression and cytokine production in pancreatic cancer patients. Clin. Cancer Res. 7, Suppl. 3, 933s-939s.

Shankaran, V., Ikeda, H., Bruce, A. T., White, J. M., Swanson, P. E., Old, L. J., and Schreiber, R. D. (2001). IFNgamma and lymphocytes prevent primary tumour development and shape tumour immuno-genicity. Nature 410, 1107-1111.

Shinkai, Y., Rathbun, G., Lam, K. P., Oltz, E. M., Stewart, V., Mendelsohn, M., Charron, J., Datta, M., Young, F., Stall, A. M., et al. (1992). RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate VDJ rearrangement. Cell 68, 855-867.

Smyth, M. J., Thia, K. Y., Street, S. E., Cretney, E., Trapani, J. A., Taniguchi, M., Kawano, T., Pelikan, S. B., Crowe, N. Y., and Godfrey, D. I. (2000a). Differential tumor surveillance by natural killer (NK) and NKT cells. J. Exp. Med. 191, 661-668.

Smyth, M. J., Thia, K. Y., Street, S. E., MacGregor, D., Godfrey, D. I., and Trapani, J. A. (2000b). Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J. Exp. Med. 192, 755-760.

Smyth, M. J., Crowe, N. Y., and Godfrey, D. I. (2001). NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int. Immunol. 13, 459-463.

Staibano, S., Mascolo, M., Tranfa, F., Salvatore, G., Mignogna, C., Bufo, P., Nugnes, L., Bonavolonta, G., and De Rosa, G. (2006). Tumor infiltrating lymphocytes in uveal melanoma: A link with clinical behavior? Int. J. Immunopathol. Pharmacol. 19, 171179.

Street, S. E., Cretney, E., and Smyth, M. J. (2001). Per-forin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97, 192-197.

Street, S. E., Trapani, J. A., MacGregor, D., and Smyth, M. J. (2002). Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J. Exp. Med. 196, 129-134.

Stutman, O. (1974). Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice. Science 183, 534-536.

Thomas, L. (1982). On immunosurveillance in human cancer. Yale J. Biol. Med. 55, 329-333.

Villegas, F. R., Coca, S., Villarrubia, V. G., Jimenez, R., Chillon, M. J., Jareno, J., Zuil, M., and Callol, L. (2002). Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer 35, 2328.

Yasunaga, M., Tabira, Y., Nakano, K., Iida, S., Ichimaru, N., Nagamoto, N., and Sakaguchi, T. (2000). Accelerated growth signals and low tumor-infiltrating lymphocyte levels predict poor outcome in T4 esophageal squamous cell carcinoma. Ann. Thorac. Surg. 70, 1634-1640.

Yoshimoto, M., Sakamoto, G., and Ohashi, Y. (1993). Time dependency of the influence of prognostic factors on relapse in breast cancer. Cancer 72, 29933001.

Zeier, M., Hartschuh, W., Wiesel, M., Lehnert, T., and Ritz, E. (2002). Malignancy after renal transplantation. Am. J. Kidney Dis. 39, E5.

Zou, W. (2005). Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat. Rev. Cancer 5, 263-274.

van den Broek, M. E., Kagi, D., Ossendorp, F., Toes, R., Vamvakas, S., Lutz, W. K., Melief, C. J., Zinkernagel, R. M., and Hengartner, H. (1996). Decreased tumor surveillance in perforin-deficient mice. J. Exp. Med. 184, 1781-1790.

This page intentionally left blank

Was this article helpful?

0 0
Nicotine Support Superstar

Nicotine Support Superstar

Stop Nicotine Addiction Is Not Easy, But You Can Do It. Discover How To Have The Best Chance Of Quitting Nicotine And Dramatically Improve Your Quality Of Your Life Today. Finally You Can Fully Equip Yourself With These Must know Blue Print To Stop Nicotine Addiction And Live An Exciting Life You Deserve!

Get My Free Ebook

Post a comment