Zhang Lin, Zhao Yibo, Dong Yan, Jiang Xiuxing
Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, China.
Department of Oncology, Southwest Hospital, Army Medical University, Chongqing, China.
Front Immunol. 2025 Jul 14;16:1621885. doi: 10.3389/fimmu.2025.1621885. eCollection 2025.
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.
髓系白血病（ML）是一种造血干细胞异常的克隆性恶性疾病。随着嵌合抗原受体T细胞（CAR-T）等新型免疫疗法的出现，ML患者的治疗效果有所改善，但仍存在重大挑战，包括严重不良事件和疾病复发。自然杀伤细胞（NK细胞）是免疫系统的“天然杀手”，不需要抗原呈递，负责识别和摧毁肿瘤细胞。一些基于NK细胞的临床试验已经开展，并在ML中取得了显著成果，且副作用较小。关键的是，在ML微环境中，与T细胞相比，NK细胞经常表现出更严重的功能耗竭，其特征是细胞毒性、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，利用基于NK细胞的疗法（如过继性转移、CAR-NK细胞）的临床研究已显示出有前景的结果和良好的安全性，突出了它们的治疗潜力。因此，开发更多基于NK细胞的策略对ML的治疗具有重要的临床意义。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。
