小胶质细胞/巨噬细胞在胶质母细胞瘤中作用的研究进展

Research advances in the role of microglia/macrophages in glioblastoma multiforme

摘要:

胶质母细胞瘤（GBM）是成人最常见的颅内恶性肿瘤，具有极强的侵袭性。此外，由于化疗药物难以通过血脑屏障和胶质母细胞瘤的耐药性，及对放疗敏感性较差等特点，故预后极差。其中肿瘤微环境的改变起到了至关重要的作用，在微环境中胶质瘤相关的小胶质细胞/巨噬细胞（GAMs）的作用正逐渐被重视。GAMs不仅有中枢系统的常驻小胶质细胞，还有来自外周的巨噬细胞。GAMs还有截然不同的两种极化类型，即抑制肿瘤生长的M1表型和促进肿瘤生长的M2表型。并且GAMs不单单和肿瘤细胞具有联系，还与微环境中其他非癌性脑细胞也有互动。该文将从GAMs的来源、极化、与肿瘤微环境中各种细胞间的相互影响阐述其在GBM中的作用，并且从靶向治疗的角度探讨其最新的研究进展。

Abstract:

Glioblastoma multiforme (GBM) is the most common intracranial malignant tumor in adults. It is characterized by strong invasiveness. In addition, its prognosis is extremely poor due to the difficulty for chemotherapeutic drugs to pass the blood-brain barrier, drug resistance of GBM, and its low sensitivity to radiotherapy. Among other factors, changes in the tumor microenvironment play a crucial role, and the role of glioma-associated microglia/macrophages (GAMs) in the microenvironment is attracting growing attention. GAMs include not only microglia from the central nervous system but also macrophages from the periphery. GAMs also involve two distinct types of polarization, namely the M1 phenotype that inhibits tumor growth and the M2 phenotype that promotes tumor growth. Furthermore, in addition to the association with tumor cells, GAMs also interact with non-cancerous brain cells in the microenvironment. In this article, we elucidate the role of GAMs in GBM regarding their source, polarization, and interactions with various cells in the tumor microenvironment, and discuss latest research advances from the perspective of targeted therapy.