The glioblastoma (GBM) tumor microenvironment consists of a heterogeneous mixture of neoplastic and non-neoplastic cells, including immune cells. Tumor recurrence following standard-of-care therapy results in a rich landscape of inflammatory cells throughout the glioma-infiltrated cortex. Immune cells consisting of glioma-associated macrophages and microglia (GAMMs) overwhelmingly constitute the bulk of the recurrent glioblastoma (rGBM) microenvironment, in comparison to the highly cellular and proliferative tumor microenvironment characteristic of primary GBM. These immune cells dynamically interact within the tumor microenvironment and can contribute to disease progression and therapy resistance while also providing novel targets for emerging immunotherapies. Within these varying contexts, histological-based assessments of immune cells in rGBM, including immunohistochemistry (IHC) and immunofluorescence (IF), offer a critical way to visualize and examine the inflammatory landscape. Here, we exhaustively review the available body of literature on the inflammatory landscape in rGBM as identified through histological-based assessments. We highlight the heterogeneity of immune cells throughout the glioma-infiltrated cortex with a focus on microglia and macrophages, drawing insights from canonical and novel immune-cell histological markers to estimate cell phenotypes and function. Lastly, we discuss opportunities for immunomodulatory treatments aiming to harness the inflammatory landscape in rGBM.
胶质母细胞瘤(GBM)肿瘤微环境由肿瘤细胞与非肿瘤细胞(包括免疫细胞)异质性混合构成。标准治疗后肿瘤复发导致胶质瘤浸润的皮质区域出现丰富的炎症细胞景观。与原发性GBM高度细胞化、增殖活跃的肿瘤微环境特征相比,由胶质瘤相关巨噬细胞和小胶质细胞(GAMMs)构成的免疫细胞在复发性胶质母细胞瘤(rGBM)微环境中占据绝对主导地位。这些免疫细胞在肿瘤微环境中动态相互作用,既可促进疾病进展和治疗抵抗,也为新兴免疫疗法提供了新的靶点。在此背景下,基于组织学的免疫细胞评估方法(包括免疫组织化学和免疫荧光技术)为观察和检测炎症景观提供了关键手段。本文系统综述了通过组织学评估揭示的rGBM炎症景观相关文献,着重阐释胶质瘤浸润皮质中免疫细胞(特别是小胶质细胞和巨噬细胞)的异质性,运用经典及新型免疫细胞组织学标志物解析细胞表型与功能。最后,探讨了针对rGBM炎症景观进行免疫调节治疗的潜在策略。