Fiche publication
Date publication
mars 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François
Tous les auteurs :
Ma Y, Aymeric L, Locher C, Mattarollo SR, Delahaye NF, Pereira P, Boucontet L, Apetoh L, Ghiringhelli F, Casares N, Lasarte JJ, Matsuzaki G, Ikuta K, Ryffel B, Benlagha K, Tesniere A, Ibrahim N, Dechanet-Merville J, Chaput N, Smyth MJ, Kroemer G, Zitvogel L
Lien Pubmed
Résumé
By triggering immunogenic cell death, some anticancer compounds, including anthracyclines and oxaliplatin, elicit tumor-specific, interferon-gamma-producing CD8(+) alphabeta T lymphocytes (Tc1 CTLs) that are pivotal for an optimal therapeutic outcome. Here, we demonstrate that chemotherapy induces a rapid and prominent invasion of interleukin (IL)-17-producing gammadelta (Vgamma4(+) and Vgamma6(+)) T lymphocytes (gammadelta T17 cells) that precedes the accumulation of Tc1 CTLs within the tumor bed. In T cell receptor delta(-/-) or Vgamma4/6(-/-) mice, the therapeutic efficacy of chemotherapy was compromised, no IL-17 was produced by tumor-infiltrating T cells, and Tc1 CTLs failed to invade the tumor after treatment. Although gammadelta T17 cells could produce both IL-17A and IL-22, the absence of a functional IL-17A-IL-17R pathway significantly reduced tumor-specific T cell responses elicited by tumor cell death, and the efficacy of chemotherapy in four independent transplantable tumor models. Adoptive transfer of gammadelta T cells restored the efficacy of chemotherapy in IL-17A(-/-) hosts. The anticancer effect of infused gammadelta T cells was lost when they lacked either IL-1R1 or IL-17A. Conventional helper CD4(+) alphabeta T cells failed to produce IL-17 after chemotherapy. We conclude that gammadelta T17 cells play a decisive role in chemotherapy-induced anticancer immune responses.
Référence
J Exp Med. 2011 Mar 14;208(3):491-503
