The Role of Immune Checkpoint Inhibitors in the Treatment of Glioblastoma: A literature Review of Current Evidence

Background: Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of many cancers but have faced many challenges in treating glioblastoma (GBM) due to the tumor's unique immune microenvironment. Methods: This literature review was conducted to explore the role of ICIs in GBM, focusing on PD-1 and PD-L1 inhibitors, and their potential in combination therapies. Studies were retrieved from PubMed, Web of Science, and a total of 26 articles were included for data extraction after applying inclusion and exclusion criteria. Results: ICIs in GBM has demonstrated limited clinical benefit despite the strong biological rationale. Large phase III trials showed that PD-1 inhibition with agents like nivolumab has not improved overall or progression-free survival, largely due to the tumor heterogeneity, immunosuppressive tumor microenvironment, and low tumor mutational burden. CTLA-4 inhibitors like ipilimumab and tremelimumab have shown limited efficacy as monotherapy, though combination or salvage strategies following failure of PD-1 showed some results, particularly in replication-repair–deficient or hypermutated gliomas. Standard chemoradiotherapy with temozolomide remains the standard of treatment, with MGMT promoter methylation as the strongest predictive biomarker. Adn PD-L2 remains underexplored as a target. Conclusion: Overall, the evidence shows that monotherapy with ICIs is insufficient in GBM, and future approaches for these agents will require case-studied patient selection, combination strategies, and integration with existing standard therapies.