CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Targeting metabolic reprogramming and epigenetic remodeling: a novel strategy to reshape the immune microenvironment in multiple myeloma.
Targeting metabolic reprogramming and epigenetic remodeling: a novel strategy to reshape the immune microenvironment in multiple myeloma.
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多发性骨髓瘤（MM）是一种高度致残的血液系统恶性肿瘤，死亡风险显著，目前正进入综合治疗时代。然而，免疫耐药仍是限制患者长期生存和有效治疗的主要障碍。两个关键的肿瘤特征——代谢重塑和表观遗传重编程——相互作用驱动这一过程。代谢改变诱导表观遗传修饰，而表观遗传调控反过来重塑代谢网络。这些过程紧密耦合，共同塑造骨髓内的肿瘤免疫微环境并促进免疫逃逸。基于这一认识，靶向代谢-表观遗传串扰可能为制定合理的联合策略提供概念框架。该框架并非代表一种已确立的临床方法，而是可能有助于识别在特定分子背景下恢复抗原呈递、改善效应T细胞和NK细胞活性、增强MM对免疫治疗敏感性的机制。它也可能为免疫治疗增敏提供机制基础。本综述描述了代谢重塑和表观遗传重编程在MM中如何相互作用，这些相互作用如何导致免疫抑制，以及它们对开发改进联合疗法的意义。
Multiple myeloma (MM) is a highly debilitating hematologic malignancy with a significant risk of mortality, now entering an era of comprehensive treatment.
However, immune resistance remains the primary obstacle limiting long-term survival and effective treatment in patients. Two critical tumor characteristics-metabolic remodeling and epigenetic reprogramming-interact to drive this process. Metabolic alterations induce epigenetic modifications, while epigenetic regulation reciprocally reshapes metabolic networks. These processes are tightly coupled, jointly shaping the tumor-immune microenvironment within the bone marrow and promoting immune evasion. Based on this understanding, targeting metabolic-epigenetic crosstalk may provide a conceptual framework for developing rational combination strategies.
Rather than representing an established clinical approach, this framework may help identify mechanisms that restore antigen presentation, improve effector T- and NK-cell activity, and enhance the sensitivity of MM to immune-based therapies in selected molecular contexts.
It may also provide a mechanistic basis for immunotherapy sensitization. This review describes how metabolic remodeling and epigenetic reprogramming interact in MM, how these interactions contribute to immune suppression, and their implications for developing improved combination therapies.
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