PT  - JOURNAL ARTICLE
AU  - Xiangdong Ye
AU  - Xueqing Wang
AU  - Wenhui Yu
AU  - Qing Yang
AU  - Yan Li
AU  - Yanxia Jin
AU  - Yanting Su
AU  - Jiaqi Song
AU  - Bo Xu
AU  - Hui Sun
TI  - Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
AID  - 10.20892/j.issn.2095-3941.2020.0278
DP  - 2021 Nov 01
TA  - Cancer Biology & Medicine
PG  - 1092--1108
VI  - 18
IP  - 4
4099  - http://www.cancerbiomed.org/content/18/4/1092.short
4100  - http://www.cancerbiomed.org/content/18/4/1092.full
SO  - Cancer Biol Med2021 Nov 01; 18
AB  - 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.