肿瘤细胞治疗研究
英文原题：Advances in T Cell-Based Cancer Immunotherapy: From Fundamental Mechanisms to Clinical Prospects.
Advances in T Cell-Based Cancer Immunotherapy: From Fundamental Mechanisms to Clinical Prospects.
T 细胞及其 T 细胞受体（TCR）在适应性免疫系统对抗病原体和肿瘤的反应中发挥关键作用。
T细胞及其T细胞受体（TCR）在适应性免疫系统抵御病原体和肿瘤的过程中发挥关键作用。然而，免疫衰老表现为T细胞功能和数量随年龄增长而下降，显著损害抗肿瘤免疫。近年来，随着对T细胞生物学认识加深及筛选技术创新，基于T细胞的癌症治疗取得了显著进展。本综述全面考察T细胞成熟机制、T细胞介导的抗肿瘤应答，以及胸腺退化对T细胞多样性和癌症预后的影响。我们讨论近期过继T细胞疗法进展，包括TIL（肿瘤浸润淋巴细胞）疗法、工程化T细胞受体（TCR-T）疗法和CAR-T 细胞疗法。值得注意的是，我们重点介绍哺乳动物细胞中DNA编码文库技术在TCR–抗原相互作用高通量筛选中的新兴应用；该技术正革新新型肿瘤抗原发现和TCR亲和力优化。综述还探讨克服实体瘤微环境挑战的策略，以及提高T细胞疗法疗效的新兴方法。随着对T细胞生物学理解不断加深、筛选技术持续进步，基于T细胞的免疫疗法有望为更广泛患者群体带来持久临床获益。
T cells and their T cell receptors (TCRs) play crucial roles in the adaptive immune system's response against pathogens and tumors. However, immunosenescence, characterized by declining T cell function and quantity with age, significantly impairs antitumor immunity. Recent years have witnessed remarkable progress in T cell-based cancer treatments, driven by a deeper understanding of T cell biology and innovative screening technologies. This review comprehensively examines T cell maturation mechanisms, T cell-mediated antitumor responses, and the implications of thymic involution on T cell diversity and cancer prognosis. We discuss recent advances in adoptive T cell therapies, including tumor-infiltrating lymphocyte (TIL) therapy, engineered T cell receptor (TCR-T) therapy, and chimeric antigen receptor T cell (CAR-T) therapy. Notably, we highlight emerging DNA-encoded library technologies in mammalian cells for high-throughput screening of TCR-antigen interactions, which are revolutionizing the discovery of novel tumor antigens and optimization of TCR affinity. The review also explores strategies to overcome challenges in the solid tumor microenvironment and emerging approaches to enhance the efficacy of T cell therapy. As our understanding of T cell biology deepens and screening technologies advances, T cell-based immunotherapies show increasing promise for delivering durable clinical benefits to a broader patient population.
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