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

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.

• Authors: Yuting Ma, Laetitia Aymeric, Clara Locher, Stephen R Mattarollo, Nicolas F Delahaye, Pablo Pereira, Laurent Boucontet, Lionel Apetoh, François Ghiringhelli, Noëlia Casares, Juan José Lasarte, Goro Matsuzaki, Koichi Ikuta, Bernard Ryffel, Kamel Benlagha, Antoine Tesnière, Nicolas Ibrahim, Julie Déchanet-Merville, Nathalie Chaput, Mark J Smyth, Guido Kroemer, Laurence Zitvogel
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 208 Issue 3 Pg. 491-503 (Mar 14 2011) ISSN: 1540-9538 [Electronic] United States
• PMID: 21383056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Interleukin-17
• Interleukin-23
• Receptors, Antigen, T-Cell, gamma-delta
• Doxorubicin
• Interferon-gamma

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• CD8-Positive T-Lymphocytes (immunology, physiology)
• Cell Death (drug effects, immunology, physiology)
• Cell Line, Tumor
• Doxorubicin (pharmacology, therapeutic use)
• Interferon-gamma (immunology, physiology)
• Interleukin-17 (immunology, physiology)
• Interleukin-23 (immunology, physiology)
• Lymphocytes, Tumor-Infiltrating (immunology, physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Receptors, Antigen, T-Cell, gamma-delta (immunology, physiology)
• Sarcoma, Experimental (drug therapy, immunology, physiopathology)
• Signal Transduction (immunology, physiology)
• T-Lymphocyte Subsets (immunology, physiology)
• Treatment Outcome