In recent years,cancer immunotherapy has attracted considerable attention in the field of biotherapy for the development of chimeric antigen receptor T (CAR-T) cell.CAR-T cells are capable of recognizing tumor cell surface antigens leading to kill tumor cells.Anti-CD19 CAR-T has achieved remarkable success in the treatment of hematopoietic malignancies.Whether it can benefit solid tumor patients to the same extent still faces great challenges,and it has been a focus of attention in immunotherapy for tumors.Compared with hematological malignancies,the microenvironment of solid tumor is more complex,and the screening of tumor specific antigen is more difficult.The infiltration of CAR-T cells from the blood system to the tumor site needs to overcome the tumor stromal barrier.Although part of CAR-T cells can infiltrate into tumor site,its function may be quickly inhibited by multiple factors in microenvironment.In this paper,authors discussed the challenges that CAR-T is facing for solid tumor treatment,including the specificity of the tumor antigen,the heterogeneity of the solid tumor antigen and the inhibitory effect of the tumor microenvironment,and proposed potential strategies to possibly overcome these hurdles.Authors believe that with the development of biotechnology,it will provide more abundant technical means to optimize the structure and function of CAR-T,and CAR-T will make breakthrough progress in the treatment of solid tumor.

Objective:To investigate the efficacy of endoscopic histoacryl injection in cirrhotic patients with newly-developed esophagogastric varices (EGV) who have previously undergone splenectomy combined with pericardial devascularization.Methods:From January 2015 to January 2020, 125 cirrhotic patients with EGV treated with endoscopic histoacryl injection at the Department of Gastroenterology, Jinling Hospital, Medical School of Nanjing University, were included in the retrospective analysis. There were 45 patients in the group of splenectomy combined with pericardial devascularization (splenectomy group for short) and 80 patients in the non-splenectomy group. The efficacy of endoscopic treatment, postoperative variceal improvement, rebleeding rate, and complications were analyzed between the two groups.Results:Endoscopic histoacryl injection was successfully completed in all 125 patients, and the median volume of histoacryl was 4.5 mL. The overall effective rate in splenectomy and non-splenectomy group was 80.0% (36/45) and 57.5% (46/80), respectively. The difference in the number of significantly effective, effective, and ineffective cases between the two groups was statistically significant (16, 20, 9 cases, and 20, 26, 34 cases, respectively, χ 2=6.469, P=0.039). Two and 14 patients developed rebleeding in the splenectomy group and non-splenectomy group, respectively; and the difference in the rebleeding rate between the two groups was statistically significant (4.4% VS 17.5%, Log-rank P=0.039). No patient died within 1 year in either group, and no serious complications such as ectopic embolism occurred. Conclusion:After splenectomy combined with pericardial devascularization in cirrhotic patients with EGV and hypersplenism, the application of histoacryl has better short-term efficacy and can significantly reduce the rebleeding rate compared with the non-splenectomy group.