Andersen Johannes K, Miletic Hrvoje, Hossain Jubayer A
Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.
Department of Pathology, Haukeland University Hospital, 5009 Bergen, Norway.
Cancers (Basel). 2022 Mar 4;14(5):1319. doi: 10.3390/cancers14051319.
Glioma refers to a group of primary brain tumors which includes glioblastoma (GBM), astrocytoma and oligodendroglioma as major entities. Among these, GBM is the most frequent and most malignant one. The highly infiltrative nature of gliomas, and their intrinsic intra- and intertumoral heterogeneity, pose challenges towards developing effective treatments. The glioma microenvironment, in addition, is also thought to play a critical role during tumor development and treatment course. Unlike most other solid tumors, the glioma microenvironment is dominated by macrophages and microglia-collectively known as tumor-associated macrophages (TAMs). TAMs, like their homeostatic counterparts, are plastic in nature and can polarize to either pro-inflammatory or immunosuppressive states. Many lines of evidence suggest that immunosuppressive TAMs dominate the glioma microenvironment, which fosters tumor development, contributes to tumor aggressiveness and recurrence and, very importantly, impedes the therapeutic effect of various treatment regimens. However, through the development of new therapeutic strategies, TAMs can potentially be shifted towards a proinflammatory state which is of great therapeutic interest. In this review, we will discuss various aspects of TAMs in the context of glioma. The focus will be on the basic biology of TAMs in the central nervous system (CNS), potential biomarkers, critical evaluation of model systems for studying TAMs and finally, special attention will be given to the potential targeted therapeutic options that involve the TAM compartment in gliomas.
胶质瘤是指一组原发性脑肿瘤，主要包括胶质母细胞瘤（GBM）、星形细胞瘤和少突胶质细胞瘤。其中，GBM最为常见且恶性程度最高。胶质瘤具有高度浸润性，且其内部和肿瘤间存在固有的异质性，这给开发有效的治疗方法带来了挑战。此外，胶质瘤微环境在肿瘤发生发展及治疗过程中也被认为起着关键作用。与大多数其他实体瘤不同，胶质瘤微环境以巨噬细胞和小胶质细胞为主——统称为肿瘤相关巨噬细胞（TAM）。TAM与其稳态对应物一样，本质上具有可塑性，可极化至促炎或免疫抑制状态。许多证据表明，免疫抑制性TAM主导着胶质瘤微环境，促进肿瘤发展，导致肿瘤侵袭性和复发，并且非常重要的是，阻碍各种治疗方案的治疗效果。然而，通过开发新的治疗策略，TAM有可能转变为促炎状态，这具有极大的治疗意义。在本综述中，我们将在胶质瘤背景下讨论TAM的各个方面。重点将放在中枢神经系统（CNS）中TAM的基础生物学、潜在生物标志物、研究TAM的模型系统的批判性评估，最后，将特别关注涉及胶质瘤中TAM区室的潜在靶向治疗选择。
