Contribution of IL-17-producing {gamma}{delta} T cells to the efficacy of anticancer chemotherapy.

Yuting Ma 1, 2 Laetitia Aymeric 1, 2 Clara Locher 1, 2 Stephen R Mattarollo 3 Nicolas F Delahaye 1 Pablo Pereira 4 Laurent Boucontet 4 Lionel Apetoh 5, 6 François Ghiringhelli 5, 6 Noëlia Casares 7 Juan José Lasarte 7 Goro Matsuzaki 8 Koichi Ikuta 9 Bernard Ryffel 10 Kamel Benlagha 11 Antoine Tesnière 12 Nicolas Ibrahim 13 Julie Déchanet-Merville 14 Nathalie Chaput 1, 15 Mark J Smyth 3 Guido Kroemer 12, 16, 17, 18, 19, * Laurence Zitvogel 1, 15, 20, *
Abstract : By triggering immunogenic cell death, some anticancer compounds, including anthracyclines and oxaliplatin, elicit tumor-specific, interferon-γ-producing CD8(+) αβ 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 γδ (Vγ4(+) and Vγ6(+)) T lymphocytes (γδ T17 cells) that precedes the accumulation of Tc1 CTLs within the tumor bed. In T cell receptor δ(-/-) or Vγ4/6(-/-) 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 γδ 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 γδ T cells restored the efficacy of chemotherapy in IL-17A(-/-) hosts. The anticancer effect of infused γδ T cells was lost when they lacked either IL-1R1 or IL-17A. Conventional helper CD4(+) αβ T cells failed to produce IL-17 after chemotherapy. We conclude that γδ T17 cells play a decisive role in chemotherapy-induced anticancer immune responses.
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Yuting Ma, Laetitia Aymeric, Clara Locher, Stephen R Mattarollo, Nicolas F Delahaye, et al.. Contribution of IL-17-producing {gamma}{delta} T cells to the efficacy of anticancer chemotherapy.. The Journal of Experimental Medecine, The Rockefeller University Press, 2011, 208 (3), pp.491-503. ⟨10.1084/jem.20100269⟩. ⟨pasteur-00576679⟩

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