Alterations in Signal Transduction in T Cells from Cancer Patients

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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. Keywords Renal Cell Carcinoma Tumor Bear Mouse Suppressor Cell Tumor Bearing Mouse Cell Antigen Receptor These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.