Interleukin-6 and vascular endothelial growth factor release by renal cell carcinoma cells impedes lymphocyte-dendritic cell cross-talk.
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)-beta1] 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.
Cabillic
F
F
UPRES 3891, Faculté de Médecine de Rennes, France. florian.cabillic@univ-rennes1.fr
Bouet-Toussaint
F
F
Toutirais
O
O
Rioux-Leclercq
N
N
Fergelot
P
P
de la Pintière
C Thomas
CT
Genetet
N
N
Patard
J-J
JJ
Catros-Quemener
V
V
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D009336:Necrosis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000276:immunology*
D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D015850:Interleukin-6; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D006861:Hydrogen Peroxide