Hypermutation as a potential predictive biomarker of immunotherapy efficacy in high-grade gliomas: a broken dream?

An interesting question arising in neuro-oncology is whether a high mutational load (a condition termed 'hypermutation') can be as immunogenic in high-grade gliomas as in other solid tumors. The most recent literature has raised the question of whether hypermutated high-grade gliomas may be 'insensitive' to immunotherapy, especially in patients pretreated with temozolomide, which is the standard of care for glioma therapy. The purpose of this review is to summarize the available evidence on hypermutated gliomas and their sensitivity to immunotherapy agents.