Immune Checkpoint Inhibitors and Glioblastoma:A Review on Current State and Future Directions

Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system. The prognosis of GBM is grim, with amedian overall survival of 14.6 months and only 6.9% of patients surviving 5 years after the initial diagnosis. Despite pooroutcomes, standard therapy of surgical resection, radiotherapy, chemotherapy, and tumor-treating fields has remained largelyunchanged. The introduction of immune checkpoint inhibitors (ICI) has been a paradigm shift in oncology, with efficacy across abroad spectrum of cancer types. Nonetheless, investigations of ICIs in both newly diagnosed and recurrent GBM have thus far beendisappointing. This lack of clinical benefit has been largely attributed to the highly immunosuppressive nature of GBM. However,immunotherapy still holds promise for the treatment of GBM, with combinatorial strategies offering hope for potentiallyovercoming these current limitations. In this review, we discuss the outcomes of clinical trials employing ICIs in patients with GBM.Afterward, we review ICI combination strategies and how these combinations may overcome the immunosuppressivemicroenvironment of GBM in the context of preclinical/clinical evidence and ongoing clinical trials.