肿瘤细胞治疗研究
英文原题：Supercharging CAR-T cells through transcriptional and epigenetic armoring.
受 CAR-T 疗法在血液系统恶性肿瘤中显著成功的启发，研究越来越聚焦于将该疗法应用于实体瘤。
受 CAR-T 治疗在血液系统恶性肿瘤中显著成功的启发，研究正日益聚焦于将这一疗法拓展至实体瘤。然而，CAR-T 疗效仍受细胞耗竭和持久性缩短的限制。转录因子和表观遗传修饰在调节 T 细胞分化与功能方面发挥关键作用；多种策略已利用这些机制，促进形成具有干细胞样特性的长寿命记忆细胞，从而增强 CAR-T 功能。本综述重点介绍关键转录因子，例如 c-Jun 和 FOXO1，它们可增强并维持 T 细胞效应功能、减少耗竭；同时讨论 TET2 和 DNMT3A 等表观遗传调节因子，其敲除可促进记忆 T 细胞亚群形成。综述进一步探讨这些因子的相互联系、下游靶点、生物学影响，以及某些候选因子的潜在应用风险，为通过转录和表观遗传干预增强 CAR-T 治疗提供全面的理论框架。
Inspired by the remarkable success of CAR-T therapy in hematologic malignancies, research is increasingly focused on adapting this treatment for solid tumors. However, CAR-T efficacy remains limited due to its exhaustion and shortened persistence. Transcription factors and epigenetic modifications play pivotal roles in modulating T cell differentiation and functionality, which have been leveraged in numerous strategies to promote the formation of long-lasting memory cells with stem-like properties and supercharging CAR-T performance. This review highlights pivotal transcriptional factors, such as c-Jun and FOXO1, which enhance and sustain T cell effector function, diminishes exhaustion, and epigenetic regulators like TET2 and DNMT3A, whose knockout promotes memory T subsets formation. We explore their interconnections, downstream targets, biological impacts, and the potential application risks of certain candidates, providing a comprehensive theoretical framework for supercharging CAR-T therapies through transcriptional and epigenetic interventions.
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