While the role of the complement system in cancer development has been studied, its involvement in the development of an anti-tumoral immune response remains poorly understood. Using cobra venom factor 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 anti-tumoral CD8+ T cell response. This immune response proved to be 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 anti-tumoral immune responses. The complement pathway could therefore be a potent therapeutic target in cancer patients to improve NK-dependent anti-tumoral immune responses.
- Received October 3, 2013.
- Revision received October 28, 2013.
- Accepted November 21, 2013.
- Copyright © 2013, American Association for Cancer Research.