Pro-inflammatory and T cell inhibitory cytokines are secreted at high levels in tumor cell cultures of human renal cell carcinoma

Objectives: The objectives of this study were to assess cytokine secretion in human renal cell carcinoma (RCC) and to identify cytokines contributing to the immunomodulatory effect of tumor cells. Methods: Cytokine secretion in the supernatant of primary tumor cell cultures (PTCC) and corresponding cell lines (CL) was assayed using ELISA. Tumor cells were characterized by morphology, immunocytochemistry, and flow-cytometric analysis. Tumor-cell-i nduced T cell activation was determined by coculture of gamma delta and alp ha beta T cell clones with tumor CL, Results: We assessed the cytokine secr etion of tumor cells from 27 PTCC and their corresponding CL (3/27) of RCC. We found that RCC predominantly produced both pro-inflammatory and T-cell- inhibitory cytokines, such as IL-8, IL-6, GM-CSF, INF-alpha, IL-10 and TGF- beta(1). CL were adapted to serum-free medium which may prove as a useful t ool in future studies of cytokine secretion in RCC. In addition, we used ga mma delta and alpha beta T cell clones to assess the immunomodulatory effec t of tumor cells from RCC and found that predominantly gamma delta T cells were activated by RCC. Conclusions: Our data suggest that RCC produce large amounts of both pro-inflammatory and T-cell-inhibitory cytokines that pote ntially could influence the immune response of the host, especially tumor-s pecific cytotoxic T cells.