外泌体通过发挥免疫调控作用影响血液肿瘤细胞生物学特性的研究进展

Research Advances on the Biological Characteristics of Hematological Malignant Cells Immunologically Regulated by Exosome——Review

微小残留病灶(minimal residual disease,MRD)是导致血液肿瘤复发及耐药的根源因素,而免疫细胞在清除微小残留病灶中发挥重要作用。多种免疫细胞具有抗肿瘤作用,但肿瘤细胞可以通过改造肿瘤微环境抑制免疫细胞的抗肿瘤作用。在肿瘤微环境中多种细胞包括免疫细胞、间充质细胞和癌细胞都可分泌外泌体(exosome)。最新研究认为,血液肿瘤细胞分泌的外泌体承载的"货物"及表面配体可调控NK细胞功能(包括迁移、活化、增殖、分泌以及NKG2D的表达)、巨噬细胞功能(迁移及分泌)及树突状细胞功能(成熟及递呈);并且调节PD-L1、CCR2的表达、CCL2的分泌及向抑制性细胞的转化。免疫细胞功能的改变最终会影响血液肿瘤的进展。

The minimal residual disease(MRD)is the origin element that caused the relapse and drug resistance of hematological malignancies,the immune cells play a great role to clear MRD.A variety of immune cells have antitumor effects.However,tumor cells antagonize anti-tumor effects by reprogramming of constituents associated with tumor environment.Many different cell types,including immune cells,mesenchymal cells and tumor cells in tumor microenvironment release exosomes.The latest researches indicate that"cargo"and surface ligands carried by exosomes secreted by hematological malignant cells not only can affect the function of natural killer cell(migration,activation,proliferation,secretion and NKG2 D expression),macrophage(migration and secretion)and dendritic cell(maturation and presentation),but also regulate the expression of PD-L1 and CCR2,CCL2 secretion and transformation of monocytes.The altered function of immune cells will eventually have effect on the progression of hematological malignancies.