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PLoS Biol. 2018 May 11;16(5):e2004990. doi: 10.1371/journal.pbio.2004990. eCollection 2018 May.

Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress.

Author information

1
Instituto de Medicina Molecular João Lobo Antunes (iMM), Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
2
The Francis Crick Institute, London, United Kingdom.
3
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université, Inserm, CNRS, Marseille, France.
4
Instituto Gulbenkian de Ciência, Oeiras, Portugal.

Abstract

Interleukin 17 (IL-17)-producing γδ T cells (γδ17 T cells) have been recently found to promote tumor growth and metastasis formation. How such γδ17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing γδ17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27- Vγ6+ γδ17 T cells via induction of oxidative stress, thereby preventing them from constituting the major source of pro-tumoral IL-17 in the tumor microenvironment. Mechanistically, we found that low expression of the antioxidant glutathione in CD27- γδ17 T cells renders them particularly susceptible to neutrophil-derived reactive oxygen species (ROS). Consistently, superoxide deficiency, or the administration of a glutathione precursor, rescued CD27- Vγ6+ γδ17 T-cell proliferation in vivo. Moreover, human Vδ1+ γδ T cells, which contain most γδ17 T cells found in cancer patients, also displayed low glutathione levels and were potently inhibited by ROS. This work thus identifies an unanticipated, immunosuppressive yet antitumoral, neutrophil/ROS/γδ17 T-cell axis in the tumor microenvironment.

Conflict of interest statement

The authors have declared that no competing interests exist.

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