Transient complement inhibition promotes a tumor-specific immune response through the implication of natural killer cells.
Although the role of the complement system in cancer development has been studied, its involvement in the development of an antitumoral immune response remains poorly understood. Using cobra venom factor (CVF) to inhibit the complement cascade via C3 molecule exhaustion in immunocompetent mice bearing B16gp33 melanoma tumors, we show that transient inhibition of the complement system allowed for the development of a more robust gp33-specific antitumoral CD8(+) T-cell response. This immune response proved to be natural killer (NK) dependent, suggesting an interaction of complement proteins with this cellular subset leading to T lymphocyte activation and enhanced cytotoxic T-cell activity against tumor cells. This study demonstrates for the first time the implication of the complement system in the development of NK-mediated cytotoxic T-cell-dependent antitumoral immune responses. The complement pathway could therefore be a potent therapeutic target to improve NK-dependent antitumoral immune responses in patients with cancer.
Authors' Affiliations: Biomed Research Center, Department of Biology, Université du Québec à Montréal, Montréal, Québec, Canada.
Valérie
V
Janelle
Marie-Pierre
MP
Langlois
Esther
E
Tarrab
Pascal
P
Lapierre
Laurent
L
Poliquin
Alain
A
Lamarre
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003176:Complement C3 / Q000276:immunology*; D051056:Complement Inactivating Agents / Q000494:pharmacology*; D004546:Elapid Venoms / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000276:immunology
D003176:Complement C3; D051056:Complement Inactivating Agents; D004546:Elapid Venoms; C016310:cobra venom factor