髓源性抑制细胞在人类白血病中的研究进展

doi:10.3877/cma.j.issn.1674-6880.2023.04.011

髓源性抑制细胞（myeloid-derived suppressor cells，MDSCs）是一种来源于骨髓造血干细胞且具有异质性的未成熟髓系细胞，在机体的免疫反应中发挥抑制调节作用^[1-2]。在健康条件下，骨髓中的祖细胞可以分化为成熟的树突状细胞（dendritic cells，DCs）、粒细胞或巨噬细胞，而在癌症、感染和自身免疫病等病理环境下，祖细胞的分化可以部分地被阻断，导致MDSCs的产生和累积^[3-4]。肿瘤与肿瘤微环境（tumor microenvironment，TME）之间复杂的相互作用导致机体处于一种免疫抑制状态，TME中具有免疫抑制功能的MDSCs、调节性T细胞（regulatory T cells，Tregs）和肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs），可以抑制正常的T细胞免疫反应，促进癌细胞的生长和免疫逃逸^[5-7]。TME中的MDSCs与肿瘤细胞相互促进，即肿瘤细胞可诱导MDSCs产生和累积，而MDSCs通过抑制免疫反应、促进血管生产和肿瘤生长与转移，在TME内构建一个适合肿瘤生长的微环境^[7-9]。大量研究表明，增多的循环和/或浸润性MDSCs与实体肿瘤和血液系统恶性肿瘤患者的不良预后密切相关，减少或清除MDSCs或者改变其抑制功能有助于恢复机体的免疫监视，这使得MDSCs有可能成为克服实体肿瘤免疫抑制微环境的潜在靶点，而靶向MDSCs的策略在血液系统恶性肿瘤的免疫治疗中虽取得了一定进展但仍然具有挑战性^[6，9-11]。因此，深入探讨MDSCs的激活、分化和功能机制有助于血液系统恶性肿瘤的免疫治疗。白血病是人类常见的一类异质性造血干细胞和祖细胞的恶性克隆性肿瘤，主要类型包括急性淋巴细胞白血病（acute lymphoblastic leukaemia，ALL）、急性髓系白血病（acute myeloid leukaemia，AML）、慢性淋巴细胞白血病（chronic lymphocytic leukaemia，CLL）和慢性髓系白血病（chronic myeloid leukaemia，CML）^[12]。在2020年全球范围内，白血病在所有新癌症中的发病率约为2.5%，病死率约为3.1%，且病死率在血液系统恶性肿瘤中最高^[13-14]。研究表明，MDSCs是一类免疫抑制性细胞，其在机体内的累积和活化可释放大量的抑制性分子，在白血病的发生发展及治疗中发挥重要的作用^[15-16]。因此，本文就MDSCs在白血病中的作用和功能以及针对MDSCs的靶向治疗进展作一综述，为白血病的防治提供新策略。

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