Abstract: Objective:To study the safety and efficacy of clinical application of autologous tumor infiltrating lymphocytes (TIL) after in vitro amplification，in combination with antiPD1 monoclonal antibody for the treatment of advanced hepatocellular carcinoma (HCC).Methods:The patients with postoperative recurrence or extrahepatic metastasis that are not operable were selected for the study.TIL were isolated from the tumor samples obtained through local resection under laparoscopy,and TIL were amplified up to 2×109 cells and administered intravenously to the patients.After TIL infusion,antiPD1 monoclonal antibody injection was followed every 21 days,and IL2 was continuously injected to maintain the activity of TIL for two weeks,and the adverse effects and treatment efficacy were evaluated.Results:TIL were successfully isolated,amplified and administered in 4 patients with advanced liver cancers.All 4 patients showed good tolerance and minor adverse effects.At present,the median followup period was 7.5 months,2 patients are under observation,one with lung metastatic lesion disappearing and the another with adrenal metastatic lesion partially necrotizing.The other 2 patients died due to high tumor load and advanced stage of tumor,and their survival time was 3 months and 6 months,respectively.Conclusion:TIL amplification and reinfusion combined with antiPD1 monoclonal antibody is safe and feasible in the treatment of advanced HCC,and the longterm efficacy requires further studies.Application of TIL amplified in vitro combined with antiPD1 monoclonal antibody is likely a hopeful new therapy for HCC.

Key words: hepatocellular carcinoma, tumor infiltrating lymphocytes, antiPD1 monoclonal antibody, immunotherapy