학술논문
Holothurian triterpene glycoside cucumarioside A2-2 induces macrophages activation and polarization in cancer immunotherapy
Document Type
Report
Author
Source
Cancer Cell International. November 24, 2023, Vol. 23 Issue 1
Subject
Language
English
Abstract
Author(s): Wen-Han Chuang[sup.1,2] , Evgeny Pislyagin[sup.3] , Liang-Yu Lin[sup.1] , Ekaterina Menchinskaya[sup.3] , Oleg Chernikov[sup.3] , Valery Kozhemyako[sup.4] , Tatiana Gorpenchenko[sup.5] , Igor Manzhulo[sup.6] , Elena Chaikina[sup.3] , Irina Agafonova[sup.3] [...]
Background Despite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors. Methods To this end, we determine the effect of a natural triterpene glycoside, cucumarioside A.sub.2-2 (CA.sub.2-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage. The polarization of CA.sub.2-2-pretreated macrophages was analyzed by flow cytometry and confocal imaging. The anti-cancer activity of CA.sub.2-2 macrophages was evaluated against 4T1 breast cancer cells and EAC cells in vitro and syngeneic mouse model in vivo. Results Incubation of murine macrophages with CA.sub.2-2 led to polarization into the M1 phenotype, and the CA.sub.2-2-pretreated macrophages could selectively target and kill various types of cancer in vitro. Notably, loading near-infrared (NIR) fluorochrome-labeled nanoparticles, MnMEIO-mPEG-CyTE777, into macrophages substantiated that M1 macrophages can target and penetrate tumor tissues in vivo efficiently. Conclusion In this study, CA.sub.2-2-polarized M1 macrophages significantly attenuated tumor growth and prolonged mice survival in the syngeneic mouse models. Therefore, ex vivo CA.sub.2-2 activation of mouse macrophages can serve as a useful model for subsequent antitumor cellular immunotherapy developments. Keywords: Holothurian triterpene glycoside, Cucumarioside A.sub.2-2, Anticancer, M1 macrophage, Immunotherapy
Background Despite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors. Methods To this end, we determine the effect of a natural triterpene glycoside, cucumarioside A.sub.2-2 (CA.sub.2-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage. The polarization of CA.sub.2-2-pretreated macrophages was analyzed by flow cytometry and confocal imaging. The anti-cancer activity of CA.sub.2-2 macrophages was evaluated against 4T1 breast cancer cells and EAC cells in vitro and syngeneic mouse model in vivo. Results Incubation of murine macrophages with CA.sub.2-2 led to polarization into the M1 phenotype, and the CA.sub.2-2-pretreated macrophages could selectively target and kill various types of cancer in vitro. Notably, loading near-infrared (NIR) fluorochrome-labeled nanoparticles, MnMEIO-mPEG-CyTE777, into macrophages substantiated that M1 macrophages can target and penetrate tumor tissues in vivo efficiently. Conclusion In this study, CA.sub.2-2-polarized M1 macrophages significantly attenuated tumor growth and prolonged mice survival in the syngeneic mouse models. Therefore, ex vivo CA.sub.2-2 activation of mouse macrophages can serve as a useful model for subsequent antitumor cellular immunotherapy developments. Keywords: Holothurian triterpene glycoside, Cucumarioside A.sub.2-2, Anticancer, M1 macrophage, Immunotherapy