Interleukin‐6 and vascular endothelial growth factor release by renal cell carcinoma cells impedes lymphocyte–dendritic cell cross‐talk

Summary Anti‐tumour T cell response requires antigen presentation via efficient immunological synapse between antigen presenting cells, e.g. dendritic cells (DC), and specific T cells in an adapted Th1 cytokine context. Nine renal cell carcinoma (RCC) primary culture cells were used as sources of tumour antigens which were loaded on DC (DC‐Tu) for autologous T cell activation assays. Cytotoxic activity of lymphocytes stimulated with DC‐Tu was evaluated against autologous tumour cells. Assays were performed with 75 grays irradiated tumour cells (Tu irr) and with hydrogen peroxide ± heat shock (Tu H 2 O 2  ± HS) treated cells. DC‐Tu irr failed to enhance cytotoxic activity of autologous lymphocytes in seven of 13 assays. In all these defective assays, irradiated tumour cells displayed high interleukin (IL)‐6 and vascular endothelial growth factor (VEGF) release. Conversely, when tumour cells released low IL‐6 levels ( n  = 4), DC‐Tu irr efficiently enhanced CTL activity. When assays were performed with the same RCC cells treated with H 2 O 2  + HS, DC‐Tu stimulation resulted in improved CTL activity. H 2 O 2  + HS treatment induced post‐apoptotic cell necrosis of tumour cells, totally abrogated their cytokine release [IL‐6, VEGF, transforming growth factor (TGF)‐β1] and induced HSP70 expression. Taken together, data show that reduction in IL‐6 and VEGF release in the environment of the tumour concomitantly to tumour cell HSP expression favours induction of a stronger anti‐tumour CTL response.