P11.04.A BREAKING THE BRAIN’S DEFENSE: A SYSTEMATIC REVIEW OF IMMUNE-EVASION MECHANISMS IN GLIOBLASTOMA AND CNS METASTASIS

Abstract INTRODUCTION Glioblastoma multiforme (GBM) is an aggressive, treatment-resistant brain tumor that evades immune detection, promoting tumor progression and metastasis within the CNS. This systematic review examines immune-evasion mechanisms in GBM and their role in CNS metastasis, focusing on immune checkpoints, tumor-associated macrophages, microglia, and exosome-mediated immune modulation. METHODS A systematic literature search following PRISMA guidelines was conducted, reviewing studies from 2010 to 2025. Databases such as PubMed, Embase, Scopus, and Web of Science were searched using keywords related to GBM, immune evasion, CNS metastasis, immune checkpoints, TAMs, microglia, and exosomes. A total of 150 studies were identified, and after screening, 30 studies met the inclusion criteria. Both preclinical and clinical studies were included. RESULTS Key immune-evasion mechanisms identified include upregulation of immune checkpoint pathways (e.g., PD-1/PD-L1, CTLA-4), polarization of tumor-associated macrophages (TAMs) towards an immunosuppressive M2 phenotype, microglial reprogramming, and exosomal secretion of immunosuppressive molecules. Cytokines like TGF-β, IL-10, and VEGF also foster immune tolerance and promote metastatic spread within the brain. CONCLUSION GBM’s immune evasion strategies are critical to its aggressiveness and resistance, especially in CNS metastasis. Our review highlights how GBM manipulates immune checkpoints, recruits immunosuppressive TAMs, and exploits the immune-privileged brain environment to promote tumor spread. Targeting these mechanisms alongside conventional therapies offers a promising approach to improve GBM patient outcomes and combat metastasis, paving the way for personalized immunotherapies that could significantly alter the prognosis for GBM patients globally.