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靶向肿瘤代谢以增强 CD8(+) T 细胞抗肿瘤免疫

英文原题:Targeting tumor metabolism to augment CD8(+) T cell anti-tumor immunity.

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Targeting tumor metabolism to augment CD8(+) T cell anti-tumor immunity.

PubMed 2024/11/20(内容时间) J Pharm Anal Q1 · IF 11.2(JCR 2025)

研究概要

基于CD8+ T细胞的免疫治疗,包括免疫检查点抑制剂和过继性细胞疗法(TIL(肿瘤浸润淋巴细胞)、T细胞受体工程T细胞(TCR-T)、CAR-T 细胞),已取得显著成功,在不同程度上延长了患者的生存期,甚至在某些病例中实现了治愈。

中文摘要

基于CD8 + T细胞的免疫治疗,包括免疫检查点抑制剂和过继性细胞疗法(TIL(肿瘤浸润淋巴细胞)、T细胞受体工程化T细胞(TCR-T)、CAR-T 细胞),已取得显著成功,在不同程度上延长了患者的生存期,甚至在某些情况下实现了治愈。然而,免疫治疗耐药和肿瘤不敏感性经常发生,导致治疗失败。近期证据强调了肿瘤细胞代谢重编程在通过分泌有害代谢物、免疫抑制性细胞因子和改变基因表达来建立免疫抑制微环境方面的重要性,这些因素抑制免疫细胞尤其是CD8 + T细胞的活性,从而逃避免疫监视。因此,靶向肿瘤细胞代谢适应以重塑免疫微环境,有望作为一种免疫调节策略来促进免疫治疗。在此,我们总结了免疫治疗与肿瘤重编程之间相互作用的最新进展,重点关注肿瘤细胞葡萄糖代谢、氨基酸代谢和脂质代谢影响CD8 + T细胞的调控机制,为免疫治疗提供有前景的代谢靶点或联合策略。

展开英文摘要原文

CD8 + T cell-based immune-therapeutics, including immune checkpoint inhibitors and adoptive cell therapies (tumor-infiltrating lymphocytes (TILs), T cell receptor-engineered T cells (TCR-T), chimeric antigen receptor T cells (CAR-T)), have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases. However, immunotherapy resistance and tumor insusceptibility frequently occur, leading to treatment failure. Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites, immune-inhibitory cytokines, and alteration of gene expression, which suppress the activity of immune cells, particularly CD8 + T cells to evade immune surveillance. Therefore, targeting tumor cell metabolic adaptations to reshape the immune microenvironment holds promise as an immunomodulatory strategy to facilitate immunotherapy. Here, we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming, focusing on the regulatory mechanisms underlying tumor cell glucose metabolism, amino acid metabolism, and lipid metabolism in influencing CD8 + T cells to provide promising metabolic targets or combinational strategies for immunotherapy.

论文信息

作者
Liu H、Yang W、Jiang J
单位
West China School of Public Health and West China Fourth Hospital, Sichuan University, Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, 610041, China.China
文献类型
综述
期刊
Journal of pharmaceutical analysis2025 May
原文标识
PubMed 40502640 · DOI 10.1016/j.jpha.2024.101150