人参皂苷Rg1通过增强T细胞效应物功能提高过继细胞治疗的抗肿瘤效果。

IF 1.5 Q3 HEMATOLOGY
Yue Liu, Lingna An, Chengfei Yang, Xiaoqi Wang, Ruihao Huang, Xi Zhang
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引用次数: 0

摘要

过继细胞疗法(ACT)在肿瘤免疫治疗中具有显著的疗效。嵌合抗原受体(CAR) T细胞疗法作为一种极具发展前景的act疗法,在治疗恶性血液肿瘤方面取得了显著的效果。然而,T细胞在免疫抑制性肿瘤微环境中的杀伤活性不足和持久性有限,限制了ACTs在癌症患者中的进一步应用。许多研究都集中在改善T细胞的细胞毒性和持久性,以达到更好的治疗效果。在本研究中,我们探讨了人参的主要药理活性成分人参皂苷Rg1在ACT中的潜在功能。我们在T细胞体外激活和扩增阶段引入Rg1,发现Rg1处理上调了两个T细胞激活标记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,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,在培养物中加入Rg1使CAR-T细胞的抗肿瘤功效增强。本研究提示人参皂苷Rg1通过增强T细胞效应物功能,为提高ACT抗肿瘤疗效提供了一条潜在途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions.

Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions.

Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions.

Ginsenoside Rg1 improves anti-tumor efficacy of adoptive cell therapy by enhancing T cell effector functions.

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.

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