Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
Brain. 2017 Jun 1;140(6):1548-1560. doi: 10.1093/brain/aww355.
Glioblastoma is the most common and most malignant primary adult human brain tumour. Diagnosis of glioblastoma carries a dismal prognosis. Treatment resistance and tumour recurrence are the result of both cancer cell proliferation and their interaction with the tumour microenvironment. A large proportion of the tumour microenvironment consists of an inflammatory infiltrate predominated by microglia and macrophages, which are thought to be subverted by glioblastoma cells for tumour growth. Thus, glioblastoma-associated microglia and macrophages are logical therapeutic targets. Their emerging roles in glioblastoma progression are reflected in the burgeoning research into therapeutics directed at their modification or elimination. Here, we review the biology of glioblastoma-associated microglia and macrophages, and model systems used to study these cells in vitro and in vivo. We discuss translation of results using these model systems and review recent advances in immunotherapies targeting microglia and macrophages in glioblastoma. Significant challenges remain but medications that affect glioblastoma-associated microglia and macrophages hold considerable promise to improve the prognosis for patients with this disease.
胶质母细胞瘤是最常见和最恶性的成人原发性人脑肿瘤。胶质母细胞瘤的诊断预后不良。治疗耐药和肿瘤复发是癌细胞增殖及其与肿瘤微环境相互作用的结果。肿瘤微环境的很大一部分由炎症浸润组成，主要由小胶质细胞和巨噬细胞组成，这些细胞被认为被胶质母细胞瘤细胞颠覆以促进肿瘤生长。因此，胶质母细胞瘤相关的小胶质细胞和巨噬细胞是合理的治疗靶点。它们在胶质母细胞瘤进展中的新兴作用反映在针对它们的修饰或消除的治疗方法的研究不断涌现。在这里，我们回顾了与胶质母细胞瘤相关的小胶质细胞和巨噬细胞的生物学，以及用于体外和体内研究这些细胞的模型系统。我们讨论了使用这些模型系统的结果转化，并回顾了针对胶质母细胞瘤中小胶质细胞和巨噬细胞的免疫疗法的最新进展。仍然存在重大挑战，但影响胶质母细胞瘤相关小胶质细胞和巨噬细胞的药物有很大的希望改善这种疾病患者的预后。
