Mutational burden and immune recognition of gliomas - Sorbonne Université
Journal Articles Current Opinion in Oncology Year : 2021

Mutational burden and immune recognition of gliomas

Abstract

Purpose of review Recent evidence suggests high tumor mutational burden (TMB-H) as a predictor of response to immune checkpoint blockade (ICB) in cancer. However, results in TMB-H gliomas have been inconsistent. In this article, we discuss the main pathways leading to TMB-H in glioma and how these might affect immunotherapy response. Recent findings Recent characterization of TMB-H gliomas showed that "post-treatment hypermutation" related to mismatch repair (MMR) deficiency is the most common mechanism leading to TMB-H in gliomas. Unexpectedly, preliminary evidence suggested no benefit with ICB as compared to chemotherapy in this population. In contrast, ICB response was reported in a subset of TMB-H gliomas associated with constitutional MMR or polymerase epsilon (POLE) defects (e.g., constitutional biallelic MMRd deficiency). In other cancers, several trials suggest increased ICB efficacy is critically associated with increased lymphocyte infiltration at baseline which is missing in most gliomas. Further characterization of the immune microenvironment of gliomas is needed to identify biomarkers to select the patients who will benefit from ICB.
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Dates and versions

hal-03474667 , version 1 (10-12-2021)

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Diego Prost, Franck Bielle, Keith L Ligon, Mehdi Touat. Mutational burden and immune recognition of gliomas. Current Opinion in Oncology, 2021, 33 (6), pp.626-634. ⟨10.1097/CCO.0000000000000787⟩. ⟨hal-03474667⟩
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