Sun Ding-Ya, Hu Yi-Jie, Li Xin, Peng Jun, Dai Zhi-Jie, Wang Shan
Xiangya School of Pharmaceutical Sciences, Department of Pharmacology, Central South University, Changsha, China.
Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, China.
Int Immunopharmacol. 2025 Jan 10;144:113392. doi: 10.1016/j.intimp.2024.113392. Epub 2024 Nov 27.
In recent years, immune cell therapy, particularly adoptive cell therapy (ACT), has shown superior therapeutic effects on hematologic malignancies. However, a challenge lies in ensuring that genetically engineered specific T cells maintain lasting anti-tumor effects within the host. The enduring success of ACT therapy hinges on the persistence of memory T (T) cells, a diverse cell subset crucial for tumor immune response and immune memory upkeep. Notably, T cell subsets at varying differentiation stages exhibit distinct biological traits and anti-tumor capabilities. Poorly differentiated T cells are pivotal for favorable clinical outcomes in ACT. The differentiation of T cells is influenced by multiple factors, including metabolism and cytokines. Consequently, current research focuses on investigating the differentiation patterns of T cells and enhancing the production of poorly differentiated T cells with potent anti-tumor properties in vitro, which is a prominent area of interest globally. This review delves into the differentiation features of T cells, outlining their distribution in patients and their impact on ACT treatment. It comprehensively explores cutting-edge strategies to boost ACT efficacy through T cell differentiation induction, aiming to unlock the full potential of T cells in treating hematologic malignancies and offering novel insights for tumor immune cell therapy.
近年来，免疫细胞疗法，尤其是过继性细胞疗法（ACT），已在血液系统恶性肿瘤治疗中展现出卓越的疗效。然而，确保基因工程改造的特异性T细胞在宿主体内维持持久的抗肿瘤作用是一项挑战。ACT疗法的持久成功取决于记忆T（Tm）细胞的持久性，Tm细胞是肿瘤免疫反应和免疫记忆维持的关键细胞亚群。值得注意的是，不同分化阶段的T细胞亚群具有不同的生物学特性和抗肿瘤能力。低分化T细胞对ACT的良好临床结果至关重要。T细胞的分化受多种因素影响，包括代谢和细胞因子。因此，当前研究聚焦于探究T细胞的分化模式，并在体外增强具有强大抗肿瘤特性的低分化T细胞的产生，这是全球关注的一个突出领域。本综述深入探讨了T细胞的分化特征，概述了它们在患者体内的分布及其对ACT治疗的影响。它全面探索了通过诱导T细胞分化来提高ACT疗效的前沿策略，旨在释放T细胞在治疗血液系统恶性肿瘤方面的全部潜力，并为肿瘤免疫细胞治疗提供新的见解。
