Advancing T-cell immunotherapy for cellular senescence and disease: Mechanisms, challenges, and clinical prospects

IF 12.5 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2025-05-22 DOI:10.1016/j.arr.2025.102783

Jizhun Wu , Lu Zhang , Zihan Zhao , Yuping Liu , Zhengxing Li , Xiaohang Feng , Lin Zhang , Xiang Yao , Jun Du , Liang Chen , Zhuolong Zhou

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Abstract

Cellular senescence is a complex biological process with a dual role in tissue homeostasis and aging-related pathologies. Accumulation of senescent cells promotes chronic inflammation, tissue dysfunction, age-related diseases, and tumor suppression. Recent advancements in immunotherapy have positioned T cell-based approaches as precision tools for the targeted clearance of senescent cells, offering a novel avenue for anti-aging interventions. This review explores the molecular mechanisms underlying cellular senescence, focusing on its immunogenic features and interactions with T cells, including T-cell activation, antigen recognition, modulation of tumor microenvironment (TME), and immune evasion strategies. Innovations such as chimeric antigen receptor (CAR)-T cells, immune checkpoint therapies, and SASP-neutralizing approaches are highlighted as breakthrough strategies for enhancing senescent cell eradication. The integration of multi-omics and artificial intelligence is further catalyzing the development of personalized therapies to amplify immune surveillance and tissue rejuvenation. Clinically, T cell-based interventions hold promise for mitigating age-related pathologies and extending healthspan, yet challenges remain in optimizing target specificity, countering immunosuppressive niches, and overcoming immune senescence in aging populations. This review synthesizes current advances and challenges, highlighting the potential of T cell immunotherapy as a cornerstone of anti-aging medicine and emphasizing the need for interdisciplinary innovation to translate preclinical findings into transformative therapies for aging and age-related diseases.

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推进t细胞免疫治疗细胞衰老和疾病：机制，挑战和临床前景

细胞衰老是一个复杂的生物学过程，在组织稳态和衰老相关病理中具有双重作用。衰老细胞的积累促进慢性炎症、组织功能障碍、年龄相关疾病和肿瘤抑制。免疫治疗的最新进展将基于T细胞的方法定位为靶向清除衰老细胞的精确工具，为抗衰老干预提供了新的途径。本文综述了细胞衰老的分子机制，重点探讨了细胞衰老的免疫原性特征及其与T细胞的相互作用，包括T细胞活化、抗原识别、肿瘤微环境（TME）调节和免疫逃避策略。嵌合抗原受体(CAR)-T细胞、免疫检查点疗法和sasp中和方法等创新被强调为增强衰老细胞根除的突破性策略。多组学和人工智能的结合进一步促进了个性化治疗的发展，以增强免疫监测和组织再生。临床上，基于T细胞的干预有望减轻与年龄相关的病理和延长健康寿命，但在优化靶点特异性、对抗免疫抑制利基和克服老龄化人群的免疫衰老方面仍存在挑战。本文综述了当前的进展和挑战，强调了T细胞免疫疗法作为抗衰老医学基石的潜力，并强调了跨学科创新的必要性，以将临床前研究结果转化为衰老和年龄相关疾病的变革性治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.