STING signaling is critical for γδ T cell-mediated tumor immunity
作者单位：Jinan University Huazhong University Of Science & Technology
会议名称：《第十四届全国免疫学学术大会》
会议日期：2021年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：γδ T cell STING Tumor immunity IFN-γ
摘 要：γδ T cells have been documented to play essential roles in tumor immunity. Our previous studies defined that γδ T cells provided early source of IFN-γ in anti-tumor immunity. However, the molecular mechanism of γδ T cell IFN-γ production is still elusive. Here, we found STING activation in both mouse and human γδ T cells enhanced IFN-γ program, which was unique and different from the signaling in macrophages and DCs. Consistently, STING-IFN-γ signaling is critical for optimal anti-tumor function of γδ T cells in vitro and in vivo. Interestingly, the intratumoral STING agonist injection mediated tumor rejection is dependent on gd T cells. Moreover, the STING downstream kinase TBK1 directly binds to Eomes, the transcription factor for IFN-γ, in γδ T cells. Finally, we found STING-TBK1 signaling in PBMC γδ T cells is impaired in cancer patients, indicating a potential biomarker for cancer. Consistently, our study identified a novel STINGTBK1-Eomes-IFN-γ axis in γδ T cells to activate anti-tumor function, and applications involving this pathway may be beneficial for tumor immunotherapy.