肿瘤微环境中单核细胞样髓源抑制细胞M-MDSCs的免疫抑制作用及其相关治疗的研究进展

Research advancements of immunosuppressive effect and treatment of monocyte-type myeloid-derived suppressor cells in tumor microenvironment

肿瘤微环境(TME)在肿瘤发生发展中发挥重要促进作用。广泛存在于TME中的髓源抑制细胞(MDSCs)是介导肿瘤免疫逃逸的主要效应细胞群。单核细胞样髓源抑制细胞(M-MDSCs)作为MDSCs中除中性粒细胞样髓源抑制细胞(PMN-MDSCs)以外的另一主要亚型,因其具备PMN-MDSCs不具备的广谱免疫抑制活性和高度可塑性,即M-MDSCs在癌症初期被招募至肿瘤部位,对T细胞、NK细胞等发挥直接免疫抑制作用,另可分化为肿瘤相关巨噬细胞(TAM)、炎症性树突状细胞(Inf-DCs)和PMN-MDSCs,从而增加肿瘤治疗难度,故研究者逐渐把目光由数量上占主导的PMN-MDSCs转向占比较少的MMDSCs。根据M-MDSCs在TME中募集迅速、分化多样和功能复杂的特点,以其为靶点的免疫疗法可从耗竭数量、干预分化和抑制功能3方面入手,以期增强临床抗肿瘤疗效。虽然国内外PMN-MDSCs研究颇丰,但聚焦于M-MDSCs的中文综述鲜有报道,本文拟从TME中M-MDSCs特点出发,首次对M-MDSCs免疫抑制作用及其靶向治疗进行综述。

Tumor microenvironment(TME)played an important role in development of tumors.Myeloid derived immunosup-pressive cells(MDSCs),which widely existed in TME,were one of main effector cell groups of tumor immune escape.Monocytic-my-eloid derived immunosuppressive cells(M-MDSCs)were other major subtypes of MDSCs besides neutrophil-like myeloid-derived sup-pressor cells(PMN-MDSCs),which had broad-spectrum immunosuppressive activity and high plasticity(diversified cell differentia-tion ability)that PMN-MDSCs did not.M-MDSCs were recruited to tumor site in early stage of cancer,and exert direct immunosup-pressive effects on T cells and NK cells and so on,which could also differentiate into tumor-associated macrophages(TAM),inflam-matory dendritic cells(Inf-DCs)and PMN-MDSCs,increasing difficulty of tumor treatment.Therefore,researchers gradually turned their attention from number-dominant PMN-MDSCs to M-MDSCs.According to characteristics of rapid recruitment,diverse differentia-tion and functional complexity in TME,treatment of targeted M-MDSCs could be started from three aspects of exhausting quantity,in-terfering differentiation and inhibiting function,which assisted clinic to achieve better antitumor efficacy.Although there were many studies on PMN-MDSCs in domestic and overseas,there was still a lack of a Chinese review focusing on M-MDSC.Based on these characteristics of M-MDSCs in TME,this article for the first time,provided an overview of immunosuppressive effect and targeted ther-apy of M-MDSCs.