肝癌发生、发展不仅是癌细胞本身的特性，更是“机体-微环境-癌细胞”三者互动的结果。固有免疫启动、调控适应性免疫，协助机体抗肿瘤。申请人前期发现：肝癌微环境中新型固有淋巴细胞亚群-黏膜相关恒定T（MAIT）细胞浸润显著下调，与其抗癌作用相关的IFN-g、穿孔素和颗粒酶B释放明显降低，癌内MAIT细胞高表达抑制性分子PD-1、Tim-3和CTLA-4。我们推测：MAIT细胞表型和功能受肝癌微环境影响，甚至向促癌方向偏移，抗癌作用受限。本项目以MAIT细胞为切入点，借助最新流式分选与高通量多光谱成像技术，系统鉴定其在肝癌微环境中的分布、表型和临床意义；阐明其迁移、趋化、耗竭与功能偏移的机制；研究其抑制、杀伤肿瘤细胞的作用；并尝试靶向PD-1等免疫抑制分子，恢复MAIT细胞抗肝癌细胞生长、侵袭功能，调控微环境免疫平衡。旨在拓展对固有免疫与肝癌微环境相互作用的认识，为临床肝癌免疫治疗提供新思路。

The invasion and metastasis characteristics of liver cancer relied more on the interactions of system-microenvironment-tumor rather than cancer cells alone. Innate immunity is another arm of immune system, which can also assist in tumor control. While our previous research indicated that the infiltration of MAIT cells in hepatocellular carcinoma significantly decreased and the secretion of IFN-g, perforin and granzyme B was significantly inhibited in MAIT cells from tumor. Moreover, we found that MAIT cells in the HCC tissues showed higher expression of immune checkpoint related molecules PD-1, Tim-3 and CTLA-4. It seems plausible that MAIT cells was suppressed in the HCC down-regulating its tumor-inhibiting ability and re-educated to promote tumor progression. In this study, our aim is to define the distribution, phenotype and the function of MAIT cells in the HCC as well as to restore the normal function of the subset by targeting PD-1 to inhibit proliferation, invasion and metastasis of HCC cells, extending the understanding of innate immunity in tumor progression and providing potential therapeutic target for clinical treatment.