肿瘤细胞治疗研究
英文原题：NK cell-based immunotherapy strategies for myeloid leukemia.
髓系白血病（ML）是一种起源于异常造血干细胞的克隆性恶性疾病。
髓系白血病（ML）是一种起源于造血干细胞异常的克隆性恶性疾病。随着CAR-T等新型免疫疗法的出现，ML患者的治疗结局得到改善，但严重不良事件和疾病复发等重大挑战依然存在。NK 细胞（NK细胞）是免疫系统中的「天然杀手」，无需抗原提呈即可识别并杀伤肿瘤细胞。一些基于NK细胞的临床研究已在ML中开展，并取得了显著成果，且副作用较低。至关重要的是，在ML微环境中，NK细胞往往比T细胞表现出更严重的功能耗竭，其特征为细胞毒性、细胞因子产生和增殖能力受损，这限制了NK细胞的抗ML疗效。然而，采用基于NK细胞疗法（如过继转移、CAR-NK细胞）的临床研究已显示出令人鼓舞的结果和良好的安全性，凸显了其治疗潜力。因此，开发更多基于NK细胞的策略对ML的治疗具有重要临床意义。在本综述中，我们系统分析了ML与NK细胞之间的关系，旨在提出更多关于NK细胞扩增和持久性增强的新方案，为ML治疗中下一代基于NK细胞的免疫疗法建立循证指南。
Myeloid leukemia (ML) is a clonal malignant disease with abnormal hematopoietic stem cells. With the emergence of novel immunotherapies, such as CAR-T, therapeutic outcomes in ML patients have improved, while significant challenges persist, including severe adverse events and disease recurrence. Natural killer cells (NK cells) are "natural killers" of the immune system that do not require antigen presentation and responsible for recognizing and destroying tumor cells. Some NK cells-based clinical experiments have been carried out and achieved remarkable results with lower side effects in ML. Crucially, within the ML microenvironment, NK cells frequently exhibit more severe functional exhaustion compared with T cells, characterized by impaired cytotoxicity, cytokine production, and proliferative capacity which limits anti-ML efficacy of NK cells. However, clinical studies utilizing NK cell-based therapies (e.g., adoptive transfer, CAR-NK cells) have demonstrated promising results with favorable safety profiles, underscoring their therapeutic potential. Therefore, developing more strategies based on NK cell is of great clinical significance for the treatment of ML. In this review, we systematically analysed the relationship between ML and NK cells, aiming to propose more novel protocols for NK cell expansion and persistence enhancement, establish evidence-based guidelines for next-generation NK cell-based immunotherapies in ML treatment.
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