Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
J Pathol. 2021 Jun;254(2):105-108. doi: 10.1002/path.5637. Epub 2021 Mar 23.
The failure of anti-VEGF/R and immune checkpoint therapies to improve overall survival in Phase III clinical trials in glioblastoma (GBM) is considered to be due in part to the prevalent immunosuppression in the GBM tumor microenvironment. Immune suppression is mediated in part by resident microglia and bone-marrow-derived myeloid cells recruited during tumor progression. A paper by Blank et al published in a recent issue of The Journal of Pathology proposes a myeloid cell-mediated mechanism that could contribute to resistance to anti-VEGF/R in GBM patients. A granulocyte-rich GBM tumor microenvironment may push the associated microglia/macrophages to exhibit an activated and immune suppressive phenotype. The identification of pro-angiogenic factors produced by microglia/macrophages and granulocytes in such a tumor microenvironment may offer new targets for improving antiangiogenic therapy of GBM beyond VEGF. Further, consideration of parameters such as IDH status, corticosteroid dosage, tumor mutational burden, gender, vascular function, and pericyte coverage could exploit current immunotherapies to the fullest to reprogram the granulocyte-rich immunosuppressive GBM tumor microenvironment to an immunostimulatory one. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
抗血管内皮生长因子/受体（VEGF/R）和免疫检查点疗法未能在胶质母细胞瘤（GBM）的 III 期临床试验中改善总生存率，部分原因被认为是 GBM 肿瘤微环境中普遍存在的免疫抑制。免疫抑制部分是由驻留的小胶质细胞和骨髓来源的髓样细胞在肿瘤进展过程中募集介导的。Blank 等人在最近一期的《病理学杂志》上发表的一篇论文提出了一种髓样细胞介导的机制，可能有助于 GBM 患者对抗 VEGF/R 的耐药性。富含粒细胞的 GBM 肿瘤微环境可能促使相关的小胶质细胞/巨噬细胞表现出激活和免疫抑制表型。在这种肿瘤微环境中鉴定由小胶质细胞/巨噬细胞和粒细胞产生的促血管生成因子，可能为超越 VEGF 的 GBM 抗血管生成治疗提供新的靶点。此外，考虑 IDH 状态、皮质类固醇剂量、肿瘤突变负担、性别、血管功能和周细胞覆盖等参数，可以充分利用当前的免疫疗法，将富含粒细胞的免疫抑制性 GBM 肿瘤微环境重新编程为免疫刺激性环境。©2021 大不列颠及爱尔兰病理学学会。由 John Wiley & Sons, Ltd. 出版。
