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人参皂苷 Rg1 通过增强 T 细胞效应功能改善过继细胞疗法的抗肿瘤疗效

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

查看英文原题

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

PubMed 2023/06/30(内容时间) Blood Sci Q2 · IF 3.6(JCR 2025)

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中文摘要

过继性细胞治疗(ACT)在肿瘤免疫治疗中展现出显著疗效。嵌合抗原受体(CAR)T细胞治疗作为最有前景的ACT之一,在治疗恶性血液肿瘤方面取得了突出效果。

然而,T细胞在免疫抑制性肿瘤微环境中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。许多研究致力于提高T细胞的细胞毒性和持久性以获得更好的治疗效果。

在本研究中,我们探索了人参皂苷Rg1——人参的主要药理活性成分——在ACT中的潜在功能。我们在T细胞体外活化和扩增阶段引入Rg1,发现Rg1处理上调了两个T细胞活化标志物CD69和CD25,同时促进T细胞向成熟状态分化。转录组测序揭示,Rg1通过增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,在培养体系中加入Rg1使CAR-T 细胞具有增强的抗肿瘤疗效。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途径。

展开英文摘要原文

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.

论文信息

作者
Liu Y、An L、Yang C、Wang X、Huang R、Zhang X
单位
Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing 400037, China.China
期刊
Blood science (Baltimore, Md.)2023 Jul
原文标识
PubMed 37546705 · DOI 10.1097/BS9.0000000000000165