Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives

作者：Hao Lin, Chaxian Liu, An-Kang Hu, Duanwu Zhang, Hui Yang, Ying Mao · 发表于：Journal of Hematology & Oncology · 年份：2024 · DOI：10.1186/s13045-024-01544-7 · 被引用次数：376 · 研究领域：Immune cells in cancer、Glioma Diagnosis and Treatment、Neuroinflammation and Neurodegeneration Mechanisms

Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and integration of medicine and engineering technology therapy, the efficacy of these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny of the inhibitory and immunosuppressive milieu within GBM has underscored the significance of cellular constituents of the GBM microenvironment and their interactions with malignant cells and neurons. Novel immune and targeted therapy strategies have emerged, offering promising avenues for advancing GBM treatment. One pivotal mechanism orchestrating immunosuppression in GBM involves the aggregation of myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAM), and regulatory T cells (Tregs). Among these, MDSCs, though constituting a minority (4–8%) of CD45 + cells in GBM, play a central component in fostering immune evasion and propelling tumor progression, angiogenesis, invasion, and metastasis. MDSCs deploy intricate immunosuppressive mechanisms that adapt to the dynamic tumor microenvironment (TME). Understanding the interplay between GBM and MDSCs pr...