| First Author | Rei M | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 34 | Pages | E3562-70 |
| PubMed ID | 25114209 | Mgi Jnum | J:213916 |
| Mgi Id | MGI:5586898 | Doi | 10.1073/pnas.1403424111 |
| Citation | Rei M, et al. (2014) Murine CD27(-) Vgamma6(+) gammadelta T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages. Proc Natl Acad Sci U S A 111(34):E3562-70 |
| abstractText | Cancer-associated inflammation mobilizes a variety of leukocyte populations that can inhibit or enhance tumor cell growth in situ. These subsets include gammadelta T cells, which can infiltrate tumors and typically provide large amounts of antitumor cytokines, such as IFN-gamma. By contrast, we report here that in a well-established transplantable (ID8 cell line) model of peritoneal/ovarian cancer, gammadelta T cells promote tumor cell growth. gammadelta 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 gammadelta T cells revealed preferential production of interleukin-17A (IL-17), rather than IFN-gamma. Consistent with this finding, both T cell receptor (TCR)delta-deficient and IL-17-deficient mice displayed reduced ID8 tumor growth compared with wild-type animals. IL-17 production by gammadelta T cells in the tumor environment was essentially restricted to a highly proliferative CD27((-)) subset that expressed Vgamma6 instead of the more common Vgamma1 and Vgamma4 TCR chains. The preferential expansion of IL-17-secreting CD27((-)) Vgamma6((+)) gammadelta 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 gammadelta T cells and SPMs that promotes tumor cell growth and thus counteracts cancer immunosurveillance. |
