Murine CD27(-) V?6(+) ?? T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages.

ABSTRACT: Cancer-associated inflammation mobilizes a variety of leukocyte populations that can inhibit or enhance tumor cell growth in situ. These subsets include ?? T cells, which can infiltrate tumors and typically provide large amounts of antitumor cytokines, such as IFN-?. By contrast, we report here that in a well-established transplantable (ID8 cell line) model of peritoneal/ovarian cancer, ?? T cells promote tumor cell growth. ?? T cells accumulated in the peritoneal cavity in response to tumor challenge and could be visualized within solid tumor foci. Functional characterization of tumor-associated ?? T cells revealed preferential production of interleukin-17A (IL-17), rather than IFN-?. Consistent with this finding, both T cell receptor (TCR)?-deficient and IL-17-deficient mice displayed reduced ID8 tumor growth compared with wild-type animals. IL-17 production by ?? T cells in the tumor environment was essentially restricted to a highly proliferative CD27((-)) subset that expressed V?6 instead of the more common V?1 and V?4 TCR chains. The preferential expansion of IL-17-secreting CD27((-)) V?6((+)) ?? T cells associated with the selective mobilization of unconventional small peritoneal macrophages (SPMs) that, in comparison with large peritoneal macrophages, were enriched for IL-17 receptor A, and for protumor and proangiogenic molecular mediators, which were up-regulated by IL-17. Importantly, SPMs were uniquely and directly capable of promoting ovarian cancer cell proliferation. Collectively, this work identifies an IL-17-dependent lymphoid/myeloid cross-talk involving ?? T cells and SPMs that promotes tumor cell growth and thus counteracts cancer immunosurveillance.

SUBMITTER: Rei M 

PROVIDER: S-EPMC4151711 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature