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 provides a compelling basis for therapeutic interventions. This review seeks to elucidate the immune regulatory mechanisms inherent in the GBM microenvironment, explore existing therapeutic targets, and consolidate recent insights into MDSC induction and their contribution to GBM immunosuppression. Additionally, the review comprehensively surveys ongoing clinical trials and potential treatment strategies, envisioning a future where targeting MDSCs could reshape the immune landscape of GBM. Through the synergistic integration of immunotherapy with other therapeutic modalities, this approach can establish a multidisciplinary, multi-target paradigm, ultimately improving the prognosis and quality of life in patients with GBM.

中文翻译：

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了解神经胶质瘤的免疫抑制微环境：机制见解和临床观点


胶质母细胞瘤（GBM）是主要的原发性恶性颅内肿瘤，由于其免疫抑制微环境而带来了巨大的挑战，从而混淆了传统的治疗干预措施。尽管已建立的治疗方案包括手术干预、放射治疗、替莫唑胺给药，以及探索免疫治疗、医学与工程技术相结合等新兴治疗方式，但这些方法的疗效仍然受到限制，导致预后结果不佳。近年来，对 GBM 内抑制和免疫抑制环境的深入研究强调了 GBM 微环境的细胞成分及其与恶性细胞和神经元相互作用的重要性。新型免疫和靶向治疗策略的出现，为推进 GBM 治疗提供了有希望的途径。 GBM 中协调免疫抑制的一种关键机制涉及骨髓源性抑制细胞 (MDSC)、神经胶质瘤相关巨噬细胞/小胶质细胞 (GAM) 和调节性 T 细胞 (Treg) 的聚集。其中，MDSC 虽然只占 GBM 中 CD45+ 细胞的少数（4-8%），但在促进免疫逃避和推动肿瘤进展、血管生成、侵袭和转移方面发挥着核心作用。 MDSC 采用复杂的免疫抑制机制来适应动态肿瘤微环境 (TME)。了解 GBM 和 MDSC 之间的相互作用为治疗干预提供了令人信服的基础。本综述旨在阐明 GBM 微环境中固有的免疫调节机制，探索现有的治疗靶点，并巩固对 MDSC 诱导及其对 GBM 免疫抑制的贡献的最新见解。 此外，该综述全面调查了正在进行的临床试验和潜在的治疗策略，展望了未来靶向 MDSC 可以重塑 GBM 的免疫格局。通过免疫治疗与其他治疗方式的协同整合，该方法可以建立多学科、多靶点的范例，最终改善 GBM 患者的预后和生活质量。