On April 1, 2014,researchers at Haiyan Liu’s group published an article entitled “IL-17A Produced by gdT Cells Promotes Tumor Growthin Hepatocellular Carcinoma” in CancerResearch.
Interleukin (IL)-17A is expressed inthe 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–de?cient mice exhibited reduced tumor growth,where as 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 CD8t T-cell responses. Furthermore, we found that IL-17Awas produced mainly byVg4 gd T cells, in so far as depleting Vg4gd T cells reduced tumor growth, where as adoptive transfer of Vg4gd T cells promoted tumor growth. Mechanistic investigations showed that IL-17A induced CXCL5 production by tumor cells to enhance the in?ltration 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 gd T cells via production of IL-1b and IL-23.Conversely, IL-17A could also enhance production of IL-1b and IL-23 in MDSC as a positive feedback. Together, our results revealed a novel mechanism involving cross-talk among gd T cells, MDSCs, and tumor cells through IL-17A production.These ?ndings offer new insights into how IL-17A in?uences tumor immunity, with potential implications for the development of tumor immunotherapy.
Shoubao Ma is the first author of the paper.Contributing author are Qiao Cheng, Yifeng Cai, Huanle Gong, Yan Wu, Xiao Yu,Liyun Shi, Depei Wu and Chen Dong. Prof. Haiyan Liu is the corresponding authorof the paper. This work has been supported by the grants from National Natural Science Foundation of China (91029703, 81072436, and 81273268), the project funding from Suzhou city (SWG0904 and SZS201109), Priority Academic Program Developmentof Jiangsu Higher Education Institutions, Qing Lan project of Jiangsu Province, Jiangsu Provincial Innovative Research Team, and Program for Changjiang Scholars and Innovative Research Team in University (IRT1075).