Abstract
Functional T cells are the central component of an effective antitumor immune response. However, in patients with renal cell carcinoma (RCC), the growth of antigenic tumors proceeds in the absence of significant T-cell responses, posing a distinct obstacle to the development of effective immunotherapy strategies and cancer vaccines. The minimum required elements of a functional antitumor immune T-cell response have been identified, including T cells that can preferentially recognize tumor-associated antigens (1). However, despite increasing evidence that T-cells recognize discrete tumor antigen, transformed cells continue to evade immune destruction, and tumors thereby progress. There is now little doubt that the immune response to tumor antigens is altered in patients with cancer (2). This rarely manifests clinically as generalized immune suppression, which may reflect the antigen specificity of the immune dysfunction in the initial stages of the disease.
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References
Finke, J. H., Rayman, P., Edinger, M., Tubbs, R. R., Stanley, J., Klein, E., and Bukowski, R. (1992) Characterization of a human renal cell carcinoma specific cytotoxic CD8+T cell line. J. Immunother.11(1), 1–11.
Finke, J., Ferrone, S., Frey, A., Mufson, A., and Ochoa, A. (1999) Where have all the T cells gone? Mechanisms of immune evasion by tumors. Immmunol. Today (20(4), 158–160.
Miescher, S., Stoeck, M., Qiao, L., Barras, C., Barrelet, L., and von Fliedner, V.(1988) Preferential clonogenic deficit of CD8-positive T-lymphocytes infiltrating human solid tumors. Cancer Res. (48(24), 6992–6998.
Alexander, J. P., Kudoh, S., Melsop, K. A., Hamilton, T. A., Edinger, M. G., Tubbs, R. R., Sica, D., Tuason, L., Klein, E., Bukowski, R. M., and Finke, J.(1993) T-cells infiltrating renal cell carcinoma display a poor proliferative response even though they can produce interleukin 2 and express interleukin 2 receptors. Cancer Res. (53(6), 1380–1387.
Wang, Q., Redovan, C., Tubbs, R., Olencki, T., Klein, E., Kudoh, S., Finke, J., and Bukowski, R. M. (1995) Selective cytokine gene expression in renal cell carcinoma tumor cells and tumor-infiltrating lymphocytes. Int. J. Cancer (61(6), 780–785.
Mizoguchi, H., O’Shea, J. J., Longo, D. L., Loeffler, C. M., McVicar, D. W., and Ochoa, A. C. (1992) Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science (258(5089), 1795–1798.
Uzzo, R. G., Clark, P. E., Rayman, P., Bloom, T., Rybicki, L., Novick, A.C., Bukowski, R. M., and Finke, J. H. (1999) Alterations in NFkappaB activation in T lymphocytes of patients with renal cell carcinoma. J. Natl. Cancer Inst. (91(8), 718–721.
Baeuerle, P. A. and Baltimore, D. (1996) NF?B: Ten years after. Cell87, 13–20.
Ullman, K. S., Northrop, J. P., Verweij, C. L., and Crabtree, G. R. (1990) Transmission of signals from the T lymphocyte antigen receptor to the genes responsible for cell proliferation and immune function: the missing link. Annu. Rev. Immunol.8, 421–452.
May, M. J. and Ghosh, S. (1998) Signal transduction through NFkB. Immunol. Today (19(2), 80–88.
Beg, A. A. and Baltimore, D. (1996) An essential role for NF-kappaB in preventing TNF-alpha induced cell death. Science274, 782–784.
Miescher, S., Whiteside, T. L., Carrel, S., and von Fliedner, V. (1986) Functional properties of tumor-infiltrating and blood lymphocytes in patients with solid tumors: effects of tumor cells and their supernatants on proliferative responses of lymphocytes. J. Immunol. (136(5), 1899–1907.
Yoshino, I., Yano, T., Murata, M., Ishida, T., Sugimachi, K., Kimura, G., and Nomoto, K. (1992) Tumor-reactive T-cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factor. Cancer Res. (52(4), 775–781.
O’Mahony, A. M., O’Sullivan, G. C., O’Conell, J., Cotter, T. G., and Collins, J.K. (1993) An immune suppressive factor derived from esophageal squamous carcinoma induced apoptosis in normal and transformed lymphoid lineage. J. Immunol.151, 4847–4856.
Finke, J. H., Zea, A. H., Stanley, J., Longo, D. L., Mizoguchi, H., Tubbs, R. R., Wiltrout, R. H., O’Shea, J. J., Kudoh, S., Klein, E., et al. (1993) Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma. Cancer Res. (53(23), 5613–5616.
Uzzo, R. G., Rayman, P., Kolenko, V., Clark, P. E., Bloom, T., Ward, A. M., Molto, L., Tannenbaum, C., Worford, L. J., Bukowski, R., Tubbs, R., Hsi, E., Bander, N. H., Novick, A. C., and Finke, J. H. (1999) Mechanisms of apoptosis in T cells from patients with renal cell carcinoma. Clin. Canc. Res.5, 1219–1229.
Gastman, B. R., Johnson, D. E., Whiteside, T. L., and Rabinowich, H. (1999) Caspase-mediated degradation of T-cell receptor zeta-chain. Cancer Res. (59(7), 1422–1427.
Uzzo, R. G., Rayman, P., Kolenko, V., Clark, P. E., Cathcart, M. E., Bloom, T., Novick, A. C., Bukowski, R. M., Hamilton, T., and Finke, J. H. Suppression of NF?B activation in T cells by soluble products from renal cell carcinomas is mediated by tumor derived gangliosides. J. Clin. Invest. in press.
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Uzzo, R.G., Kolenko, V., Novick, A.C., Finke, J.H. (2001). Assessment of T-Cell Immune Dysfunction in Patients with Renal Cell Carcinoma. In: Mydlo, J.H. (eds) Renal Cancer. Methods in Molecular Medicine, vol 53. Humana, Totowa, NJ. https://doi.org/10.1385/1-59259-144-2:361
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DOI: https://doi.org/10.1385/1-59259-144-2:361
Publisher Name: Humana, Totowa, NJ
Print ISBN: 978-0-89603-828-8
Online ISBN: 978-1-59259-144-2
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