Department of Neurosciences, Monash University, Central Clinical School, Melbourne, Vic, Australia; Department of Physiology, The University of Melbourne, Melbourne, Vic, Australia.
Department of Physiology, The University of Melbourne, Melbourne, Vic, Australia.
J Neuroimmunol. 2019 Jul 15;332:138-146. doi: 10.1016/j.jneuroim.2019.04.010. Epub 2019 Apr 20.
Gliomas are the most prevalent tumours of the central nervous system and present with high morbidity and mortality. The most common and most aggressive form of glioma is glioblastoma multiforme, of which patients have a median survival time of only 12 to 15 months. Current treatment options are limited and have a small impact on clinical outcome and prognosis. There is accumulating evidence that microglia, the immunocompetent cells of the central nervous system, and the purinergic P2X7 receptor (P2X7R) may contribute to tumour progression and pathology. Importantly, P2X7R on both tumour cells and infiltrating microglia is overexpressed in animal and human glioma cultures. Factors released by glioma cells and P2X7R activation recruit microglia into the largely immunosuppressive tumour microenvironment where they have been demonstrated to contribute to either tumour proliferation or tumour suppression. It is likely that P2X7R mediates a range of microglia effector functions in the glioma setting, potentially increasing tumour growth and proliferation. This review evaluates current evidence on the roles of microglia and P2X7R in glioma pathogenesis. Understanding the nature, mechanisms and outcomes of microglia and P2X7R activation in gliomas is necessary for the development of more therapies with increased efficacy and specificity.
神经胶质瘤是中枢神经系统最常见的肿瘤，具有高发病率和死亡率。最常见和最具侵袭性的神经胶质瘤是多形性胶质母细胞瘤，患者的中位生存时间仅为 12 至 15 个月。目前的治疗选择有限，对临床结果和预后的影响较小。越来越多的证据表明，小胶质细胞（中枢神经系统的免疫活性细胞）和嘌呤能 P2X7 受体（P2X7R）可能与肿瘤进展和病理学有关。重要的是，在动物和人类神经胶质瘤培养物中，肿瘤细胞和浸润的小胶质细胞上的 P2X7R 过度表达。神经胶质瘤细胞释放的因子和 P2X7R 的激活将小胶质细胞募集到主要是免疫抑制的肿瘤微环境中，在那里已经证明它们有助于肿瘤增殖或肿瘤抑制。P2X7R 可能在神经胶质瘤环境中介导一系列小胶质细胞效应功能，从而潜在地增加肿瘤生长和增殖。本综述评估了小胶质细胞和 P2X7R 在神经胶质瘤发病机制中的作用的现有证据。了解小胶质细胞和 P2X7R 在神经胶质瘤中的激活的性质、机制和结果，对于开发更有效和更具特异性的治疗方法是必要的。
