近年来，肝癌的临床治疗策略已取得突破性的进展，以化疗，靶向治疗及免疫治疗为代表的肝癌系统治疗显著改善了晚期肝癌患者的生存。但无论化疗还是新兴的免疫治疗，都存在临床缓解率低，治疗后肿瘤耐药抵抗的问题。课题组前期研究成果发现，化疗激活的ID1/c-Myc 信号能够诱导肝癌细胞发生磷酸戊糖代谢重编程，促进其对奥沙利铂耐药。进一步预实验探索提示，奥沙利铂耐药肝癌细胞可能通过c-Myc/PD-L1信号逃逸CD8+CTL介导的免疫杀伤，并招募骨髓来源的免疫抑制细胞MDSCs，“塑造”免疫耐受微环境，促进肿瘤进展及转移。本课题拟从肝癌耐药细胞“改造”肿瘤免疫微环境的角度，阐明奥沙利铂耐药肝癌细胞免疫逃逸，进展及转移的分子机制，为克服肝癌化疗抵抗，免疫耐受提供新的理论基础和临床治疗策略。

Recently, systematic treatments, including chemotherapy, molecular target therapy as well as immunotherapy have achieved an encouraging survival benefit in advanced hepatocellular carcinoma. However, the low response rates and drug resistance significantly compromise the prognosis of HCC patients. In our previous study, we demonstrated that after repeated chemotherapy, the activation of ID1/c-Myc signaling conferred chemoresistance to oxaliplatin via pentose phosphate pathway. Further preliminary experiments revealed that oxaliplatin-resistant HCC cells could escape CD8+ cytotoxic T cell-dependent antitumor immunity through up-regulating of c-Myc/PD-L1 pathway. More importantly, oxaliplatin-resistant HCC cells could probably recruit myeloid-derived suppressor cells (MDSCs) in tumor microenvironment thus induce adaptive immune tolerance.The aim of the present study is to investigate the molecular mechanism in which oxaliplatin-resistant HCC cells evading host immune surveillance and killing by using cell and animal models as well as human HCC samples.This is a piloted study involving the role of oxaliplatin-resistant HCC cells on the remodeling of tumor immune microenvironment , which will contribute potential therapeutic targets to chemo-resistance and immune tolerance for HCC．