Liver cancer is one of the common malignant tumors in clinic, and the incidence rate has been increasing year by year. Most patients are diagnosed at the advanced stage, and the prognosis is poor. The occurrence and development of hepatocellular carcinoma is closely associated with immune elimination, balance and escape. In recent years, checkpoint inhibitors have been used in clinic and immune checkpoint inhibitors have made extensive progress and application in clinical research, which has brought a significant opportunity to improve the survival rate of patients with advanced liver cancer. However, HCC patients develop immunotherapy resistance afterwords. The poor drug response to tumor cells is a serious problem affecting the clinical prognosis. This review briefly summarizes the potential mechanism of innate resistance and acquired resistance in immunotherapy of liver cancer.

Objective:To analyze the efficacy and safety of FOLFOX-hepatic arterial infusion chemotherapy (HAIC) combined with targeted immunotherapy for initial unresectable hepatocellular carcinoma.Methods:A retrospective analysis was conducted on the data of initial unresectable hepatocellular carcinoma patients who visited Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2022 to June 2023. A total of 51 patients were enrolled, including 47 males and 4 females, with the age of (56.1±10.7) years. All 51 patients received HAIC combined with immune targeted therapy. After each HAIC combined with immune targeted therapy, the efficacy was evaluated according to the modified response evaluation cirteria in solid tumor (mRECIST). Objective response rate and disease control rate were calculuted. The conversion surgery rate and adverse events during treatment were recorded. Follow up patients' disease progression and survival status, and meanwhile analyze prognosis.Results:According to mRECIST assessment, the number of patients with complete remission, partial remission, disease stability, and disease progression were 4 (7.8%), 27 (52.9%), 14 (27.4%), and 6 (11.8%), respectively. The disease remission rate was 60.8%(31/51), and the disease control rate was 88.2%(45/51). After HAIC combined with immune targeted therapy, 13 patients underwent liver cancer resection, with a surgical conversion rate of 25.5%(13/51). The median progression free survival of 51 patients was 14.2 months, and the median overall survival has not yet been reached. The progression free survival rates of 51 patients at 6 and 12 months were 90.2% and 64.7%, respectively, and the cumulative survival rates at 6 and 12 months were 100% and 86.3%, respectively. During the treatment period, all patients experienced various degrees of adverse reactions, 38(75.5%) patients were grade 1-2 adverse accidents, which could be relieved and controlled after corresponding treatment.Conclusion:FOLFOX-HAIC combined with targeted immunotherapy provides an effective and safe treatment option for unresectable hepatocellular carcinoma, offering surgical resection opportunities for unresectable hepatocellular carcinoma patients.