Immunotherapy for glioblastoma: the promise of combination strategies

Glioblastoma (GBM) treatment has remained almost unchanged for more than 20 years. The current standard of care involves surgical resection (if possible) followed by concomitant radiotherapy and chemotherapy. In recent years, immunotherapy strategies have revolutionized the treatment of many cancers, increasing the hope for GBM therapy. However, mostly due to the high, multifactorial immunosuppression occurring in the microenvironment, the poor knowledge of the neuroimmune system and the presence of the blood-brain barrier, the efficacy of immunotherapy in GBM is still low. Recently, new strategies for GBM treatments have employed immunotherapy combinations and have provided encouraging results in both preclinical and clinical studies. The lessons learned from clinical trials highlight the importance of tackling different arms of immunity. In this review, we aim to summarize the preclinical evidence regarding combination immunotherapy in terms of immune and survival benefits for GBM management. The outcomes of recent studies assessing the combination of different classes of immunotherapeutic agents (e.g., immune checkpoint blockade and vaccines) will be discussed. Finally, future strategies to ameliorate the efficacy of immunotherapy and facilitate clinical translation will be provided to address the unmet medical needs of GBM.

Automated summary

The treatment of glioblastoma (GBM) has remained unchanged for over 20 years. Immunotherapy strategies have shown promise in revolutionizing cancer treatment, but the efficacy in GBM is hampered by immunosuppression, limited understanding of the neuroimmune system, and the blood-brain barrier. Recent studies have demonstrated that combination immunotherapy approaches have yielded encouraging results in both preclinical and clinical settings, highlighting the importance of targeting different arms of immunity. This review aims to summarize the preclinical evidence and discuss the outcomes of recent studies on combination immunotherapy for GBM management, as well as propose future strategies to improve efficacy and address the unmet medical needs of GBM.