Liu Yue, An Lingna, Yang Chengfei, Wang Xiaoqi, Huang Ruihao, Zhang Xi
Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing 400037, China.
Department of Urology, Xinqiao Hospital, Army Military Medical University, Chongqing 400037, China.
Blood Sci. 2023 Jun 30;5(3):170-179. doi: 10.1097/BS9.0000000000000165. eCollection 2023 Jul.
Adoptive cell therapy (ACT) has emerged with remarkable efficacies for tumor immunotherapy. Chimeric antigen receptor (CAR) T cell therapy, as one of most promising ACTs, has achieved prominent effects in treating malignant hematological tumors. However, the insufficient killing activity and limited persistence of T cells in the immunosuppressive tumor microenvironment limit the further application of ACTs for cancer patients. Many studies have focused on improving cytotoxicity and persistence of T cells to achieve improved therapeutic effects. In this study, we explored the potential function in ACT of ginsenoside Rg1, the main pharmacologically active component of ginseng. We introduced Rg1 during the in vitro activation and expansion phase of T cells, and found that Rg1 treatment upregulated two T cell activation markers, CD69 and CD25, while promoting T cell differentiation towards a mature state. Transcriptome sequencing revealed that Rg1 influenced T cell metabolic reprogramming by strengthening mitochondrial biosynthesis. When co-cultured with tumor cells, Rg1-treated T cells showed stronger cytotoxicity than untreated cells. Moreover, adding Rg1 to the culture endowed CAR-T cells with enhanced anti-tumor efficacy. This study suggests that ginsenoside Rg1 provides a potential approach for improving the anti-tumor efficacy of ACT by enhancing T cell effector functions.
过继性细胞疗法（ACT）已成为肿瘤免疫治疗中具有显著疗效的方法。嵌合抗原受体（CAR）T细胞疗法作为最有前景的ACT之一，在治疗恶性血液肿瘤方面取得了显著效果。然而，免疫抑制性肿瘤微环境中T细胞杀伤活性不足和持久性有限，限制了ACT在癌症患者中的进一步应用。许多研究都集中在提高T细胞的细胞毒性和持久性以实现更好的治疗效果。在本研究中，我们探索了人参主要药理活性成分人参皂苷Rg1在ACT中的潜在作用。我们在T细胞的体外激活和扩增阶段引入Rg1，发现Rg1处理上调了两个T细胞激活标志物CD69和CD25，同时促进T细胞向成熟状态分化。转录组测序显示，Rg1通过加强线粒体生物合成影响T细胞代谢重编程。当与肿瘤细胞共培养时，经Rg1处理的T细胞比未处理的细胞表现出更强的细胞毒性。此外，在培养中添加Rg1赋予CAR-T细胞增强的抗肿瘤功效。本研究表明，人参皂苷Rg1通过增强T细胞效应功能为提高ACT的抗肿瘤疗效提供了一种潜在方法。
