Human accessory cells activate fresh, normal, tumor-distant T lymphocytes but not tumor-infiltrating T lymphocytes to lyse autologous tumor cells in a primary cytotoxic T lymphocyte assay in renal cell carcinoma

Objectives: Search for an ideal responderT-lymphocyte source for adoptive T -lymphocyte therapy in renal cell carcinoma (RCC). Methods: Cytotoxic T-lymphocyte (CTL) activity of (a) normal, tumor-distant , renal T lymphocytes, (b) tumor-infiltrating T lymphocytes and (c) periphe ral blood T lymphocytes against autologous tumor epithelial cells (EC) of 1 0 patients with organ-confined, primary RCC was analyzed in a primary CTL a ssay. Freshly enriched T lymphocytes were cultured with or without autologo us, mitomycin-C-treated normal or tumor EC in the presence or absence of an tigen-presenting cells (APC) for 7 days. Results: Both tissue T-lymphocyte populations displayed a similar CD4:CD8 r atio (1:1). Elevated CD62L coexpression of CD4+T lymphocytes in normal, tum or-distant, renal tissue resulted in a significantly higher transient T-cel l activation than that seen in renal tumor tissue (46 vs. 27%; p = 0.002). All trials to induce significant lysis of autologous, renal tumor EC in tum or-infiltrating and peripheral blood T lymphocytes failed. Only when normal , tumor-distant, renal T lymphocytes were stimulated by autologous APC and tumor EC was significant autologous tumor EC lysis obtained (mean 14%; p < 0.05). Costimulation by anti-CD3 (mean 21%; p < 0.05) or interleukin-2 (mea n 31%; p < 0.05) further increased tumor EC lysis significantly. Conclusions: Increased turnover of T lymphocytes in normal, tumor-distant, renal tissue was associated with a higher yield of pre-CTL which can be tra nsformed into a functionally active effector T-cell pool by stimulation via antigen plus APC. Thus, tumor-distant renal tissue has to be included in t he tissue-sampling procedure for adoptive immunotherapy. Copyright (C) 2001 S. Karger AG, Basel.