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Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10.
Huang, Mu-Yang; Chen, Yu-Chi; Lyu, Wen-Yu; He, Xin-Yu; Ye, Zi-Han; Huang, Can-Yu; He, Xin-Ling; Chen, Xiuping; Chen, Xiaobing; Zhang, Baoxian; Kai, Guoyin; Zhang, Xiaolei; Li, Ting; Huang, Mingqing; Lu, Jin-Jian.
Afiliación
  • Huang MY; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China.
  • Chen YC; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China.
  • Lyu WY; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China.
  • He XY; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China.
  • Ye ZH; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China.
  • Huang CY; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China.
  • He XL; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China.
  • Chen X; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China; Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao Special Administrative Region of China
  • Chen X; Increasepharm (Hengqin) Innovative Medicine Institute Limited, Zhuhai, China.
  • Zhang B; Increasepharm (Hengqin) Innovative Medicine Institute Limited, Zhuhai, China.
  • Kai G; 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.
  • Zhang X; 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.
  • Li T; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China. Electronic address: tingli@um.edu.mo.
  • Huang M; College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China. Electronic address: hmq1115@126.com.
  • Lu JJ; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region of China; Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao Special Administrative Region of China
Pharmacol Res ; 198: 106988, 2023 Dec.
Article en En | MEDLINE | ID: mdl-37984507
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Antígeno B7-H1 Límite: Animals / Humans Idioma: En Revista: Pharmacol Res Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Antígeno B7-H1 Límite: Animals / Humans Idioma: En Revista: Pharmacol Res Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos