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Original Article | Open Access

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

Xiangdong Ye1,2,*, Xueqing Wang1,*, Wenhui Yu1, Qing Yang1, Yan Li1, Yanxia Jin3, Yanting Su1, Jiaqi Song1, Bo Xu1, Hui Sun1,4 ( )
College of Life Sciences, Wuhan University, Wuhan 430071, China
Department of Biochemistry and Molecular Biology, Institute of Biomedical research, College of Basic Medicine, Hubei University of Medicine, Shiyan 442000, China
Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization, Hubei Normal University, Huangshi 435002, China
Hubei Province key Laboratory of Allergy and Immunology; Wuhan University, Wuhan 430071, China

*These authors contributed equally to this work.

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Abstract

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.

Keywords

immunotherapyHepatocellular carcinomaAAGLanti-PD-1lymphocyte infiltration

Electronic Supplementary Material

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Cancer Biology & Medicine
Volume 18 Issue 4,
November 2021
Pages 1092-1108
DOI: 10.20892/j.issn.2095-3941.2020.0278
Cite this article:
Ye X, Wang X, Yu W, et al. Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver. Cancer Biology & Medicine, 2021, 18(4): 1092-1108. https://doi.org/10.20892/j.issn.2095-3941.2020.0278

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Received: 04 June 2020
Accepted: 08 September 2020
Published: 01 November 2021
©2021 Cancer Biology & Medicine.

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