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

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...

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Autores principales:	Xiangdong Ye, Xueqing Wang, Wenhui Yu, Qing Yang, Yan Li, Yanxia Jin, Yanting Su, Jiaqi Song, Bo Xu, Hui Sun
Formato:	article
Lenguaje:	EN
Publicado:	China Anti-Cancer Association 2021
Materias:	hepatocellular carcinoma aagl anti-pd-1 immunotherapy lymphocyte infiltration Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/662947d485384ab4bcc695a0a465f295
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spelling	oai:doaj.org-article:662947d485384ab4bcc695a0a465f2952021-11-30T11:27:44ZSynergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver2095-394110.20892/j.issn.2095-3941.2020.0278https://doaj.org/article/662947d485384ab4bcc695a0a465f2952021-11-01T00:00:00Zhttp://www.cancerbiomed.org/index.php/cocr/article/view/1811https://doaj.org/toc/2095-3941Objective: 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.Xiangdong YeXueqing WangWenhui YuQing YangYan LiYanxia JinYanting SuJiaqi SongBo XuHui SunChina Anti-Cancer Associationarticlehepatocellular carcinomaaaglanti-pd-1immunotherapylymphocyte infiltrationNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Biology & Medicine, Vol 18, Iss 4, Pp 1092-1108 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatocellular carcinoma aagl anti-pd-1 immunotherapy lymphocyte infiltration Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hepatocellular carcinoma aagl anti-pd-1 immunotherapy lymphocyte infiltration Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xiangdong Ye Xueqing Wang Wenhui Yu Qing Yang Yan Li Yanxia Jin Yanting Su Jiaqi Song Bo Xu Hui Sun Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
description	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.
format	article
author	Xiangdong Ye Xueqing Wang Wenhui Yu Qing Yang Yan Li Yanxia Jin Yanting Su Jiaqi Song Bo Xu Hui Sun
author_facet	Xiangdong Ye Xueqing Wang Wenhui Yu Qing Yang Yan Li Yanxia Jin Yanting Su Jiaqi Song Bo Xu Hui Sun
author_sort	Xiangdong Ye
title	Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
title_short	Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
title_full	Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
title_fullStr	Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
title_full_unstemmed	Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
title_sort	synergistic effects of aagl and anti-pd-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver
publisher	China Anti-Cancer Association
publishDate	2021
url	https://doaj.org/article/662947d485384ab4bcc695a0a465f295
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Synergistic effects of AAGL and anti-PD-1 on hepatocellular carcinoma through lymphocyte recruitment to the liver

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