Fiche publication
Date publication
mars 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BORG Christophe
,
Pr GHIRINGHELLI François
,
Dr LADOIRE Sylvain
,
Dr VINCENT Julie
,
Dr VEGRAN Frédérique
,
Pr MASSON David
,
Dr REBE Cédric
,
Dr BRUCHARD Mélanie
,
Dr HICHAMI Aziz
,
Dr CHALMIN Fanny
,
Dr DERANGERE Valentin
Tous les auteurs :
Chalmin F, Mignot G, Bruchard M, Chevriaux A, Vegran F, Hichami A, Ladoire S, Derangere V, Vincent J, Masson D, Robson SC, Eberl G, Pallandre JR, Borg C, Ryffel B, Apetoh L, Rebe C, Ghiringhelli F
Lien Pubmed
Résumé
Although Th17 cells are known to promote tissue inflammation and autoimmunity, their role during cancer progression remains elusive. Here, we showed that in vitro Th17 cells generated with the cytokines IL-6 and TGF-beta expressed CD39 and CD73 ectonucleotidases, leading to adenosine release and the subsequent suppression of CD4(+) and CD8(+) T cell effector functions. The IL-6-mediated activation of the transcription factor Stat3 and the TGF-beta-driven downregulation of Gfi-1 transcription factor were both essential for the expression of ectonucleotidases during Th17 cell differentiation. Stat3 supported whereas Gfi-1 repressed CD39 and CD73 expression by binding to their promoters. Accordingly, Th17 cells differentiated with IL-1beta, IL-6, and IL-23 but without TGF-beta did not express ectonucleotidases and were not immunosuppressive. Finally, adoptive transfer of Th17 cells induced by TGF-beta and IL-6 promoted tumor growth in a CD39-dependent manner. Thus, ectonucleotidase expression supports the immunosuppressive fate of Th17 cells in cancer.
Référence
Immunity. 2012 Mar 23;36(3):362-73
