Emerging Biomarkers for Immunotherapy in Glioblastoma.

Abstract

Simple SummaryImmunotherapy has shown clinical benefits in several solid cancers; still, glioblastoma remains very challenging to treat. Glioblastoma is the most frequent brain cancer and displays great heterogeneity. The standard of care has remained the same for over fifteen years, and to overcome the therapeutic limitations, emerging immune correlates of therapy responses and improved prognosis should be further developed for a more personalized therapy approach and increased clinical responses.Immunotherapy has shown clinical benefits in several solid malignancies—in particular, melanoma and non-small cell lung cancer. However, in other solid tumours such as glioblastoma (GBM), the response to immunotherapy has been more variable, and except for anti-PD-1 for patients with microsatellite instable (MSI)+ cancers, no immunotherapy is currently approved for GBM patients. GBM is the most common and most aggressive brain cancer with a very poor prognosis and a median overall survival of 15 months. A few prognostic biomarkers have been identified and are used to some extent, but apart from MSI, no biomarkers are used for patient stratification for treatments other than the standard of care, which was established 15 years ago. Around 25% of new treatments investigated in GBM are immunotherapies. Recent studies indicate that the use of integrated and validated immune correlates predicting the response and guiding treatments could improve the efficacy of immunotherapy in GBM. In this review, we will give an overview of the current status of immunotherapy and biomarkers in use in GBM with the main challenges of treatment in this disease. We will also discuss emerging biomarkers that could be used in future immunotherapy strategies for patient stratification and potentially improved treatment efficacy.