Abstract
Patients with cancer have a suppressed immune response characterized, by a decreased delayed type hypersensitivity, a diminished cytotoxic function of T and NK cells and a decreased ability to produce certain cytokines (1–3).Tumor infiltrating lymphocytes (TIL) which appear to have tumor specific reactivity in some cancers, also show a decrease in proliferation to different antigenic stimuli (4) and a markedly decreased clonogenicity (5). The basis for this immunosuppressed state is poorly understood. Possible explanations have ranged from the presence of suppressor cells (6) to the production of suppressor factors by tumors (7). The impact of this immunosupressed state on immunotherapeutic approaches to treat cancer is not known. However, several murine tumor models have shown that the use of low dose radiation or low dose cyclophosphamide before the infusion of T cells enhances the anti-tumor effect. These approaches have been incorporated in human immunotherapy trials. Low dose cyclophosphamide has been administered before the transfer of activated cells in an attempt to block “suppressor cells” and hopefully improve the anti-tumor response. Similarly, sublethal irradiation appears to enhance the therapeutic effect of activated T cells. Still the overall therapeutic response to adoptive immunotherapy continues to be low suggesting that mechanisms other than the presence of suppressor cells might explain the decreased efficacy.
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Broder, S. and Waldmann, T. A. The suppressor-cell network in cancer. N. Eng. J. Med, 299: 1281–1284, 1978.
Hersh, E.M., and Oppenheim, J.J. Impaired in vitro lymphocyte transformation in Hodgkin’s disease. N. Engl. J. Med. 273: 1006–1012, 1965.
Hellstrom, L., Warner, G.A., Hellstrom K.E. and Sjogren, H.O. Sequential studies on cell-mediated tumor immunity and blocking serum activity in ten patients with malignant melanoma. Int. J. Cancer, 11: 280–292, 1973.
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. H. T-cells infiltrating renal cell carcinoma display a poor proliferative response even though they can produce IL-2 and express IL2 receptors. Cancer Res. 53:1380–1387, 1993.
Miescher, S., Stoeck, M., Quiao, L., Barras, C., Barrelet, L. and on Fliedner, V. Preferential clonogenic deficit of CD8-positive T-lymphocytes infiltrating human solid tumors. Cancer Res. 48: 6992–6998, 1988.
North, R.J., and I., Bursuker, 1984. Generation and decay of the immune response tot aprogressive fibrosarcoma. I. Ly-1 +2- suppressor T cells down-regulate the generation of Ly-1–2+ effector T cells. J. Exp. Med. 159: 1295–1311, 1984.
Ebert, E.C., Roberts, A.I., O’ Connell, S.M., Robertson, F. M. and Nagase, H. Characterization of an immunosuppressive factor derived from colon cancer cells. J. Immunol, 138: 2161–2168, 1987.
Nakagomi, H., Peterson, M., Magnusson, I., Juhlin, C., Matsuda, M., Mellstedt, H., Taupin, J-L, Vivier, E., Anderson, P., Kiesswling, R. Decreased expression of the signal transducing z chains in tumor-infiltrating T cells and NK cells of patients with colorectal carcinoma. Cancer Res. 53: 5610, 1993.
Roth, J.A., Osborne, B.A., and Ames, R.S. Immunoregulatory factors derived from human tumors. J. Immunol, 130: 303–308, 1983.
Yoshino, Il, Yano, T., Murata, M., Ishida, T., Sugimachi, K., Kimura, G. and Nomoto K. Tumor-reactive T-cells accumulate in lung cancer tissues but fail to respond due to tumor cell-derived factors. Cancer Res. 52: 775–781, 1992.
Fu, Y.X., Watson, G.A., Kasahara, M., Lopez, D.M. The role of tumor-derived cytokines onthe immune system of mice bearing a mammary adenocarcinoma. I. Induction of regulatory macrophages in normal mice by the in vivo administration of rGM-CSF. J Immunol. 146 (2): 783–789, 1991.
Ghosh, P., Sica, A., Young, H.A., Ye, J., Franco, J.L., Wiltrout, R.H., Longo, D.L., Rice, N.R. and Komschlies, K.L. Alterations in NFKB/Rel family of proteins in splenic T cells from tumor-bearign mice and reversal following therapy. Cancer Res. 54: In Press, 1994.
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© 1995 Springer-Verlag New York Inc.
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Zea, A.H., Longo, D.L., Finke, J.H., Bukowski, R.M., Ochoa, A.C. (1995). Alterations in Signal Transduction in T Cells from Cancer Patients. In: Biology of Renal Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2536-2_7
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DOI: https://doi.org/10.1007/978-1-4612-2536-2_7
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