Immunotherapy for Glioblastoma: A Focus on PD-1/PD-L1 Inhibitors

Glioblastoma is the most common and lethal type of tumor of the central nervous system, with an average survival of 15 months after first diagnosis. Immune checkpoint inhibitors (ICIs) have been largely investigated for their ability to harness the immune system to combat tumors. However, their efficacy varies a lot depending on tumor type. In glioblastoma, PD-1/PD-L1 immunotherapy has been explored in various studies; however, the unique immunosuppressive environment in the brain and the presence of the blood–brain barrier as well as the large intratumoral heterogeneity have limited its efficacy considerably. In order to improve the clinical efficacy of ICIs, it is important to delve into the different factors affecting the response rate in GBM. Herewith, we summarize the most common causes of resistance to anti-PD-1/PD-L1 immunotherapy as well as possible ways of enhancing its efficacy, particularly through combination with other therapeutic agents in the preclinical and clinical setting. Furthermore, we provide an insight into the most promising methods for modulating the blood–brain barrier, as well as the growing role of molecular imaging and radiogenomics in this field.