Nitric oxide synthase 2 is involved in the pro-tumorigenic potential of γδ17 T cells in melanoma. (2nd August 2016)

• Record Type: Journal Article
• Authors: Douguet, Laetitia; Bod, Lloyd; Lengagne, Renée; Labarthe, Laura; Kato, Masashi; Avril, Marie-Françoise; Prévost-Blondel, Armelle
• Is Part Of: Oncoimmunology. Volume 5:Number 8(2016)
• Publication Date: 2016-08-02
• Subjects: Interleukin 17 -- melanoma -- NOS2 -- pro-tumor functions -- γδ T cells; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2016.1208878
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: γδ T lymphocytes may exert either protective or tumor-promoting functions in cancer, mostly based on their polarization toward interferon (IFN)-γ or interleukin (IL)-17 productions, respectively. Here, we demonstrate that γδ T cells accelerate the spontaneous metastatic melanoma development in a model of transgenic mice for the human RET oncogene (Ret mice). We identify unanticipated roles of inducible nitric oxide synthase (NOS2) in favoring the recruitment of pro-tumor γδ T cells within the primary tumor. γδ T cells isolated from Ret mice deficient for NOS2 produced more IFNγ and less IL-17 than their counterparts from Ret mice. By supporting IL-17 production by γδ T cells, NOS2 leads to the recruitment of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and metastasis formation. NOS2 also reduces the cytotoxicity of γδ T cells toward melanoma cells. Finally, we detected NOS2 expressing γδ T cells in the primary tumor and tumor-draining lymph nodes in Ret mice, but also in human melanoma. Overall our results support that this NOS2 autocrine expression is responsible for the polarization of γδ T cells toward a pro-tumor profile.