RT Journal Article
SR Electronic
T1 Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
JF Cancer Biology & Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 1092
OP 1108
DO 10.20892/j.issn.2095-3941.2020.0278
VO 18
IS 4
A1 Xiangdong Ye
A1 Xueqing Wang
A1 Wenhui Yu
A1 Qing Yang
A1 Yan Li
A1 Yanxia Jin
A1 Yanting Su
A1 Jiaqi Song
A1 Bo Xu
A1 Hui Sun
YR 2021
UL http://www.cancerbiomed.org/content/18/4/1092.abstract
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.