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Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10

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资源类型：
Pubmed体系：
作者：
Huang Mu-Yang[1] * ; Chen Yu-Chi[1] ; Lyu Wen-Yu[1] ; He Xin-Yu[1] ; Ye Zi-Han[1] ; Huang Can-Yu[1] ; He Xin-Ling[1] ; Chen Xiuping[1,2] ; Chen Xiaobing[3] ; Zhang Baoxian[3] ; Kai Guoyin[4] ; Zhang Xiaolei[5] ; Li Ting[1] ; Huang Mingqing[6] ; Lu Jin-Jian[1,2,7,8,*1] ;
机构： [1]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China [2]Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao Special Administrative Region of China [3]Increasepharm (Hengqin) Innovative Medicine Institute Limited, Zhuhai, China [4]Zhejiang Provincial International S&T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health, School of Pharmaceutical Sciences, The Third Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China [5]National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China [6]College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China [7]MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao Special Administrative Region of China [8]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macao Special Administrative Region of China
出处：
DOI： 10.1016/j.phrs.2023.106988
ISSN：

关键词： PD-1/PD-L1 Ginsenoside Rh2 T cells Tumor microenvironment Combination treatment

摘要：
Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

基金：
This study was supported by the Science and Technology Development Fund, Macau SAR (File No. 0053-2021-AGJ and 0015-2022-A1), the Joint Foundation of Guangdong and Macau for Science and Technology Innovation (2022A0505020024), the National Natural Science Foundation of China (File No. 81973516), the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (GuangdongHong Kong-Macau Joint Lab, File No. 2020B1212030006), as well as the Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine, University of Macau (File No. SKL-QRCMIRG2023-011).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 药学
最新[2025]版：
大类 | 2 区 医学
小类 | 1 区 药学
第一作者：
第一作者机构： [1]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China
通讯作者：
通讯机构： [1]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China [2]Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao Special Administrative Region of China [7]MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao Special Administrative Region of China [8]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Macao Special Administrative Region of China [*1]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China
推荐引用方式(GB/T 7714)：
Huang Mu-Yang,Chen Yu-Chi,Lyu Wen-Yu,et al.Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10[J].Pharmacological research.2023,198:106988.doi:10.1016/j.phrs.2023.106988.
APA：
Huang Mu-Yang,Chen Yu-Chi,Lyu Wen-Yu,He Xin-Yu,Ye Zi-Han...&Lu Jin-Jian.(2023).Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10.Pharmacological research,198,
MLA：
Huang Mu-Yang,et al."Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10".Pharmacological research 198.(2023):106988

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