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Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy
Authors: Ma, Yuting
Aymeric, L. (Laetitia)
Locher, C. (Clara)
Mattarollo, S.R. (Stephen R.)
Delahaye, N.F. (Nicolas F.)
Pereira, P. (Pablo)
Boucontet, L. (Laurent)
Apetoh, L. (Lionel)
Ghiringhelli, F. (François)
Noelia, C. (Casares)
Lasarte, J.J. (Juan José)
Matsuzaki, G. (Goro)
Ikuta, K. (Koichi)
Ryffel, B. (Bernard)
Benlagha, K. (Kamel)
Tesniere, A. (Antoine)
Ibrahim, N. (Nicolás)
Dechanet-Mervill, J. (Julie)
Chaput, N. (Nathalie)
Smyth, M.J. (Mark J.)
Kroemer, G. (Guido)
Zitvogel, L. (Laurence)
Keywords: Antineoplastic Agents/pharmacology
Interleukin-17/physiology
Receptors, Antigen, T-Cell, gamma-delta/physiology
Sarcoma, Experimental/immunology
T-Lymphocyte Subsets/physiology
Issue Date: 2011
Publisher: Rockefeller University Press
Publisher version: http://jem.rupress.org/content/208/3/491
ISSN: 1540-9538
Citation: Ma Y, Aymeric L, Locher C, Mattarollo SR, Delahaye NF, Pereira P, et al. Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy. J Exp Med 2011 Mar 14;208(3):491-503.
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.
Permanent link: http://hdl.handle.net/10171/21722
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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