免疫治疗是提高晚期转移性肾癌患者生存的有效手段，解除调节性肿瘤浸润免疫细胞所形成的免疫抑制微环境在此过程中发挥重要作用。项目申请人前期研究发现肿瘤组织中C型凝集素样受体Clec-2阳性DCs 高浸润(Oncotarget 2016)及其配体糖蛋白Podoplanin 高表达(Cancer Sci 2016)在肾癌进展中发挥关键作用。进一步研究发现：肾癌Clec-2+DCs高浸润与瘤内CD8+T细胞功能抑制密切相关，并预示患者不良生存；肾癌细胞Podoplanin能通过活化Clec-2+DCs分泌IDO抑制CD8+T细胞增殖。本项目拟在前期基础上，分析肾癌细胞Podoplanin活化肿瘤浸润Clec-2+DCs分泌IDO抑制CD8+T细胞功能的分子机制及其促进肾癌进展的功能意义，建立调节性肿瘤浸润DCs钝化CD8+T细胞功能促进肾癌进展的分子调控和干预模型，为开发针对性免疫治疗药物奠定基础。

For patients with metastatic renal cell carcinoma (RCC), immunotherapy is an appropriate choice which would bring about survival benefits. Within this procedure, the inhibition of immunoregulatory tumor infiltrating lymphocytes and the transformation of immunosuppressed tumor microenvironment is very important. Our recent works revealed that high tumoral infiltration of dendritic cells (DCs) expressing C-type lectin-like receptor 2 (Clec-2) and high expression of Clec-2’s ligand podoplanin in tumor cells could both play pivotal roles in RCC progression. Moreover, high Clec-2+DCs infiltration correlated with intratumoral CD8+ T cell dysfunction and could predict dismal RCC patient survival. We also found that podoplanin could stimulate Clec-2+DCs to secrete IDO, thus inhibiting CD8+T cell proliferation and activation. Based on these results, we tend to further explore the molecular mechanism of podoplanin/Clec-2+DCs interaction, analyzing the downstream IDO mediated CD8+T Cell suppression and its significance in RCC progression. We hope that this project would help the survival prediction and the development of personalized immunotherapies for RCC patients.