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

Files in This Item:
Thumbnail
File
JEM201114208.pdf
Description
Size
2.73 MB
Format
Adobe PDF


Statistics and impact
0 citas en
0 citas en

Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.