肿瘤细胞治疗研究
英文原题：Trained immunity in the treatment for haematological malignancy.
训练免疫作为一种新兴的治疗策略，通过调控固有免疫细胞的表观遗传和代谢重编程，赋予其长期抗肿瘤记忆，为血液系统恶性肿瘤的免疫治疗提供了新途径。
训练免疫作为一种新兴的治疗策略，通过调控固有免疫细胞的表观遗传和代谢重编程，赋予其长期抗肿瘤记忆，为血液系统恶性肿瘤的免疫治疗提供了新途径。本文系统概述了β-葡聚糖、卡介苗（BCG）和细胞因子等诱导剂训练巨噬细胞和自然杀伤（NK）细胞等关键效应细胞的机制。进一步分析了衰老——包括机体衰老和细胞衰老——如何在多个层面特异性削弱相关通路的疗效，从造血干细胞功能和细胞内信号传导到肿瘤微环境，从而系统性损害训练免疫的诱导效率、效应持久性和安全性。在此基础上，本文评估了细胞因子诱导记忆样（CIML）NK细胞等策略的临床转化前景及相关风险，包括移植物抗宿主病（GVHD），并提出了旨在克服衰老相关缺陷的具体、可检验的转化思路。我们认为，要充分实现该疗法在老年血液系统恶性肿瘤患者中的潜力，未来工作必须聚焦于开发能够规避或逆转免疫衰老的个体化训练方案。
Trained immunity, an emerging treatment strategy, confers long-term anti-tumour memory by modulating epigenetic and metabolic reprogramming of innate immune cells, offering a novel pathway for immunotherapy of haematological malignancies. This article systematically outlines the mechanisms by which inducers such as β-glucan, Bacille Calmette-Guérin (BCG) and cytokines train key effector cells including macrophages and natural killer (NK) cells. It further analyses how ageing-encompassing both organismal ageing and cellular senescence-specifically undermines the efficacy of relevant pathways at multiple levels, from haematopoietic stem cell function and intracellular signalling to the tumour microenvironment, thereby systematically impairing the induction efficiency, durability of effect, and safety of trained immunity. Building on this, the article evaluates the clinical translation prospects and associated risks, including graft-versus-host diseases (GVHDs), of strategies such as cytokine-induced memory-like (CIML) NK cells, and proposes concrete, testable translational ideas aimed at overcoming ageing-related defects. We argue that to realise the full potential of this therapy in elderly patients with haematological malignancies, future work must focus on developing individualised training protocols capable of circumventing or reversing immunosenescence.
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