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Synergistic effects of aagl and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver

Cancer Biology & Medicine 2021年第4期18卷 1092-1108页

作者： Xiangdong Ye Xueqing Wang Wenhui Yu Qing Yang Yan Li Yanxia Jin Yanting Su Jiaqi Song Bo Xu Hui Sun College of Life Sciences Wuhan UniversityWuhan 430071China Department of Biochemistry and Molecular Biology Institute of Biomedical researchCollege of Basic MedicineHubei University of MedicineShiyan 442000China Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization Hubei Normal UniversityHuangshi 435002China Hubei Province key Laboratory of Allergy and Immunology Wuhan UniversityWuhan 430071China

Objective:Therapy for hepatocellular carcinoma(HCC)is a major challenge,and targeted therapies provide only a modest benefit in terms of overall survival.Treatment with antibodies to programmed cell death protein 1(PD-1)/PD-L1 can restore the functions of tumor-infiltrating T cells in HCC and has shown clinical efficacy in 20%of patients with advanced HCC.Novel approaches are urgently needed to treat HCC and to augment the efficacy of immunotherapy.Methods:Tumor-bearing mice were treated with Agrocybe aegerita galectin(aagl)alone or in combination with anti-PD-1,and the tumor sizes and lifespans of mice were determined.Transcriptome analysis,cytokine analysis,flow cytometry analysis of the number and proportion of immune cell subsets in the liver and spleen,and molecular and cellular analyses of tumors were used to define the underlying mechanisms.Results:aagl significantly inhibited the growth of liver tumors in a dose-dependent manner.Furthermore,aagl increased the expression of multiple cytokines and chemokines in tumor-bearing mouse livers;this effect was associated with the activation and migration of T cells and macrophages,in agreement with the in vitro results.Importantly,the aggregation of T cells and macrophages induced by aagl in tumor-bearing mouse livers clearly enhanced the response to PD-1 blockade immunotherapy.Conclusions:The results showed that aagl induced the activation and migration of lymphocytes to the liver,and that the combination of aagl and anti-PD-1 may be a promising strategy for HCC treatment.

关键词： Hepatocellular carcinoma aagl anti-PD-1 immunotherapy lymphocyte infiltration

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