| First Author | Ma S | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 7 | Pages | 1969-82 |
| PubMed ID | 24525743 | Mgi Jnum | J:210532 |
| Mgi Id | MGI:5571414 | Doi | 10.1158/0008-5472.CAN-13-2534 |
| Citation | Ma S, et al. (2014) IL-17A produced by gammadelta T cells promotes tumor growth in hepatocellular carcinoma. Cancer Res 74(7):1969-82 |
| abstractText | Interleukin (IL)-17A is expressed in the tumor microenvironment where it appears to contribute to tumor development, but its precise role in tumor immunity remains controversial. Here, we report mouse genetic evidence that IL-17A is critical for tumor growth. IL-17A-deficient mice exhibited reduced tumor growth, whereas systemic administration of recombinant mouse IL-17A promoted the growth of hepatocellular carcinoma. The tumor-promoting effect of IL-17A was mediated through suppression of antitumor responses, especially CD8(+) T-cell responses. Furthermore, we found that IL-17A was produced mainly by Vgamma4 gammadelta T cells, insofar as depleting Vgamma4 gammadelta T cells reduced tumor growth, whereas adoptive transfer of Vgamma4 gammadelta T cells promoted tumor growth. Mechanistic investigations showed that IL-17A induced CXCL5 production by tumor cells to enhance the infiltration of myeloid-derived suppressor cells (MDSC) to tumor sites in a CXCL5/CXCR2-dependent manner. IL-17A also promoted the suppressive activity of MDSC to reinforce suppression of tumoral immunity. Moreover, we found that MDSC could induce IL-17A-producing gammadelta T cells via production of IL-1beta and IL-23. Conversely, IL-17A could also enhance production of IL-1beta and IL-23 in MDSC as a positive feedback. Together, our results revealed a novel mechanism involving cross-talk among gammadelta T cells, MDSCs, and tumor cells through IL-17A production. These findings offer new insights into how IL-17A influences tumor immunity, with potential implications for the development of tumor immunotherapy. |
