Restoration of antitumor immunity through selective inhibition of myeloid derived suppressor cells by anticancer therapies.
Fiche publication
Date publication
juillet 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François, Dr LADOIRE Sylvain
Tous les auteurs :
Apetoh L, Vegran F, Ladoire S, Ghiringhelli F
Lien Pubmed
Résumé
Accumulating evidence suggests that the success of some anticancer therapies not only relies on their direct cytotoxicity on tumor cells but also on their ability to promote anticancer immune responses. However, immunosuppressive cells such as Myeloid Derived Suppressor Cells (MDSC) that are generated during tumor progression blunt antitumor immune responses and thus represent a major obstacle to the clinical implementation of immunotherapy protocols. We have recently identified 5-Fluorouracil (5-FU) as an anticancer agent that selectively induced MDSC apoptotic cell death in vitro and in vivo. The elimination of MDSC by 5-FU increased IFNgamma secretion by tumor specific CD8(+) T cells infiltrating the tumor and promoted T-cell dependent antitumor responses in vivo, suggesting that some anticancer therapies can reverse tumor-mediated immunosuppression. Here, we review the molecular pathways leading to the induction of MDSC in cancer and discuss how different anticancer agents successfully target these cells in vivo, thereby restoring potent anticancer immunity.
Référence
Curr Mol Med. 2011 Jul 1;11(5):365-72.