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靶向 T 细胞代谢重编程以增强抗肿瘤应答

英文原题:Targeting Metabolic Reprogramming of T-Cells for Enhanced Anti-Tumor Response.

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Targeting Metabolic Reprogramming of T-Cells for Enhanced Anti-Tumor Response.

PubMed 2022/05/09(内容时间) Biologics Q2 · IF 4.5(JCR 2025)

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中文摘要

癌症免疫治疗是有效的抗癌治疗选择,其中一种策略是调节T细胞介导的抗肿瘤免疫应答。T细胞是适应性免疫细胞,负责细胞介导的免疫,长期以来被认为是免疫介导抗肿瘤反应的关键调控者。研究显示,细胞代谢改变可抑制或增强T细胞活性。此外,T细胞激活期间的代谢重编程有助于形成不同的分化状态,可能使其建立持久的细胞介导抗肿瘤免疫。然而,肿瘤微环境(TME)会导致T细胞发生代谢耗竭,并形成多项功能障碍。目前,改善T细胞疗法(包括嵌合抗原受体CAR-T 细胞疗法)疗效的多种机制性方案仍有待明确。改变这些细胞的代谢特性并将其用于癌症免疫治疗,可能提高其抗肿瘤活性和治疗效力。本综述介绍癌细胞与T细胞的代谢重编程、免疫代谢调控相关信号机制、TME对T细胞代谢适能的影响,以及通过靶向T细胞代谢重编程增强抗肿瘤应答的策略。

展开英文摘要原文

Cancer immunotherapy is an effective treatment option against cancer. One of the approaches of cancer immunotherapy is the modification of T cell-based anti-tumor immune responses. T-cells, a type of adaptive immune response cells responsible for cell-mediated immunity, have long been recognized as key regulators of immune-mediated anti-tumor immunity. T-cell activities have been reported to be suppressed or enhanced by changes in cell metabolism.

Moreover, metabolic reprogramming during activation of T cells is required for the development of distinct differentiation profiles of these cells, which may allow the development of long-term cell-mediated anti-tumor immunity.

However, T cells have been shown to undergo metabolic exhaustion in tumor microenvironment (TME) as it poses several obstacles to their function. Applications of several mechanistic solutions to improve the efficacy of T cell-based therapies including chimeric antigen receptor (CAR) T cell therapy are yet to be determined.

Modifying the metabolic properties of these cells and employing them in cancer immunotherapy is a potential strategy for improving their anti-tumor activity and therapeutic efficacy. To give an insight, in this review paper, we endeavoured to cover metabolic reprogramming in cancer and T cells, signalling mechanisms involved in immuno-metabolic regulation, the effects of the TME on T cell metabolic fitness, and targeting metabolic reprogramming of T cells for an enhanced anti-tumor response.

论文信息

作者
Dabi YT、Andualem H、Degechisa ST、Gizaw ST
单位
Department of Medical Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
文献类型
综述
期刊
Biologics : targets & therapy2022
原文标识
PubMed 35592358 · DOI 10.2147/BTT.S365490