Impaired cytolytic activity in peripheral blood T cells from renal cell carcinoma patients |
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Authors: | Crocenzi Todd S Tretter Christopher P G Schwaab Thomas Schned Alan R Heaney John A Cole Bernard F Fisher Jan L Ernstoff Marc S |
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Affiliation: | Uro-Oncology Program, Norris Cotton Cancer Center and the Section of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756-0001, USA. |
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Abstract: | Classic T lymphocyte cytotoxicity is mediated through the T cell receptor (TCR). Defects in TCR signal transduction and cytolytic activity have been reported in tumor infiltrating T lymphocytes. We hypothesized that impaired cytotoxicity occurs in peripheral blood T cells from renal cell carcinoma (RCC) that can be reversed by exposure to rhIL-2. Peripheral blood mononuclear cells (PBMC) from 29 RCC patients and 29 healthy volunteers were isolated and cultured in the absence or presence of 10 IU/ml rhIL-2. A redirected cytotoxicity assay that requires TCR signal transduction was used with chromium-labeled P815 target cells, effector PBMC and anti-CD3 antibody. Target cell lysis was measured in "lytic units" (LU). Mean LU from RCC patients was lower than that of healthy volunteers (105.8 LU vs. 194.6 LU, P = 0.025). Exposure to rhIL-2 increased T cell-mediated lysis in both groups. Disruption of T cell cytotoxicity in RCC patients can be overcome by exposure to rhIL-2. |
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Keywords: | Cytolytic T lymphocytes TCR signal transduction Redirected cytotoxicity Renal cell carcinoma |
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