肿瘤细胞不仅表达PD-L1分子抑制T细胞活化，也分泌TGFβ激活间质细胞下游信号通路抑制T细胞瘤内浸润。两种机制相互协同介导免疫逃逸，但PD-L1和TGFβ在肝癌免疫逃逸中的作用及其调控机制尚不清楚。我们在前期研究发现转录因子MEF2D与肝癌发生发展密切相关的基础上，进一步发现MEF2D明显促进肝癌细胞PD-L1和TGFβ的表达，且肝癌细胞MEF2D通过抑制CD8+T细胞介导的抗肿瘤免疫进而促进肿瘤生长。据此猜测：MEF2D可促使肝癌细胞表达TGFβ和PD-L1，抑制T细胞肿瘤浸润并削弱其细胞杀伤能力，从而促进肝癌免疫逃逸。本课题拟证实MEF2D对TGFβ和PD-L1表达的调控作用并探索内在分子机制；并采用小鼠肝脏原位移植瘤模型及MEF2D肝脏条件性敲除小鼠DEN诱导肝癌模型，探讨上述调控关系在肝癌免疫逃逸过程中的作用，为肝癌治疗提供新的靶点和策略。

On the one hand, tumor cells could suppress T cells activation via expressing programmed death ligand 1 (PD-L1). On the other hand, tumor cells could secrete transforming growth factor beta (TGFβ), which contributes to exclusion of T cells via activating TGFβ singling pathway in stromal cells in tumor microenvironment. However, the role and potential regulation mechanism of PD-L1 and TGFβ in hepatocellular carcinoma (HCC) are unclear. Our previous study found that transcription factor Myocyte Enhancer Factor 2D (MEF2D), which is related to HCC progress, significantly promotes PD-L1 and TGFβ expression in HCC. Moreover, we found that MEF2D attenuates CD8+ T cell-mediated anti-tumor immunity to promote HCC progression. Based on our previous results and literature evidences, we speculate：MEF2D may be a key suppressor of anti-tumor immunity dependent on regulating PD-L1 and TGFβ expression, which inhibit tumor cell killing ability and tumor infiltration ability of T cells, respectively. Next, we plan to further investigate the regulation mechanism; and use orthotopic tumor allograft model and DEN-induced HCC in liver-specific MEF2D knockout mice to further investigate the role of MEF2D regulating PD-L1 and TGFβ expression on immune escape of HCC, and providing a new strategy in HCC therapy.