Barriers to overcoming immunotherapy resistance in glioblastoma

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, known for its poor prognosis and high recurrence rate. Current standard of care includes surgical resection followed by combined radiotherapy and chemotherapy. Although immunotherapies have yielded promising results in hematological malignancies, their successful application in GBM remains limited due to a host of immunosuppressive factors unique to GBM. As a result of these roadblocks, research efforts have focused on utilizing combinatorial immunotherapies that target networks of immune processes in GBM with promising results in both preclinical and clinical trials, although limitations in overcoming the immunosuppressive factors within GBM remain. In this review, we aim to discuss the intrinsic and adaptive immune resistance unique to GBM and to summarize the current evidence and outcomes of engineered and non-engineered treatments targeted at overcoming GBM resistance to immunotherapy. Additionally, we aim to highlight the most promising strategies of targeted GBM immunotherapy combinatorial treatments and the insights that may directly improve the current patient prognosis and clinical care.

Automated summary

Glioblastoma multiforme (GBM) is a common malignant brain tumor with a poor prognosis and high recurrence rate. Immunotherapies have shown promise in treating hematological malignancies, but their effectiveness in GBM is limited by unique immunosuppressive factors. However, research has shown that combinatorial immunotherapies targeting immune processes in GBM have had promising results. This review aims to discuss the immune resistance in GBM and summarize the current evidence and outcomes of treatments to overcome GBM's resistance to immunotherapy.