如何抑制肿瘤免疫逃逸从而提高免疫治疗的疗效是目前临床肿瘤免疫治疗的重点和难点。近年来大量研究表明肿瘤微环境中髓系来源抑制性细胞（MDSCs）的趋化募集是肿瘤免疫逃逸的重要原因。但是MDSCs趋化募集的调控机制尚不清楚。我们前期的研究发现，人肝癌组织中MDSCs的浸润数量显著增加，RIP3的表达水平与MDSCs的浸润数量呈正相关。干涉RIP3可以降低MDSCs在肝癌组织的趋化募集。本项目在前期研究基础上，运用大量临床标本和多种动物模型、细胞模型，深入探讨: 1)RIP3介导MDSCs趋化募集的作用及对肝癌进展和预后的临床意义。2)RIP3调控MDSCs趋化募集的关键趋化因子和受体，阐明RIP3调控MDSCs趋化募集促进肝癌免疫逃逸的机制。3)开展RIP3抑制剂联合趋化因子抗体抗肝癌免疫治疗的研究。该课题的完成将对寻找肝癌免疫治疗新靶点，研发肝癌免疫治疗药物，提高肿瘤免疫治疗疗效具有重要意义。

How to inhibit tumor immune escape and improve antitumor efficacy is currently the focus and difficulty of cancer immunotherapy. In recent years, it becomes clear that the recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment plays an important role in tumor immune escape. However, the mechanisms of MDSCs recruitment into the TME remain unclear. Our previous studies demonstrated that the abundance of MDSCs in HCC tissues was significantly higher than matched adjacent liver tissues. Concordant overexpression of RIP3 and MDSCs markers was observed in HCC patients. Furthermore, the chemotaxis assay proved that knockdown of RIP3 in hepatoma cells could effectively inhibit MDSCs recruitment. Based on discoveries above, we aim to clarify the exact mechanisms of MDSCs recruitment by utilization of plenty clinical samples and various animal and cell modes. We mainly focus on three controversies: 1) The role of RIP3 in MDSC recruitment by clinical samples and function assays, and the clinical significance for progression and prognosis of HCC. 2) The key chemokine-receptor axis regulated by RIP3 in MDSCs recruitment, elucidate the molecular mechanisms of MDSC recruitment regulated by RIP3 in HCC immune escape. 3) Conduct the study of RIP3 inhibitor in HCC immunotherapy. In conclusion, accomplishment of this research program will be of great significance in discovering novel immunotherapy targets, developing immunotherapy drugs and improving antitumor efficacy of HCC immunotherapy.