Department of Oncology, AUSL Bologna, Bologna, Italy.
Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Immunotherapy. 2022 Jul;14(10):799-813. doi: 10.2217/imt-2021-0277. Epub 2022 Jun 7.
A high tumor mutational burden and mismatch repair deficiency are observed in 'hypermutated' high-grade gliomas (HGGs); however, the molecular characterization of this distinct subtype and whether it predicts the response to immune checkpoint inhibitors (ICIs) are largely unknown. Pembrolizumab is a valid therapeutic option for the treatment of hypermutated cancers of diverse origin, but only a few clinical trials have explored the activity of ICIs in hypermutated HGGs. HGGs appear to differ from other cancers, likely due to the prevalence of subclonal versus clonal neoantigens, which are unable to elicit an immune response with ICIs. The main aim of this review is to summarize the current knowledge on hypermutation in HGGs, focusing on the broken promises of tumor mutational burden and mismatch repair deficiency as potential biomarkers of response to ICIs.
在“高度突变”的高级别神经胶质瘤（HGG）中观察到高肿瘤突变负担和错配修复缺陷；然而，这种独特亚型的分子特征及其是否预测对免疫检查点抑制剂（ICI）的反应在很大程度上尚不清楚。派姆单抗是治疗多种来源的高度突变癌症的有效治疗选择，但只有少数临床试验探讨了 ICI 在高度突变 HGG 中的活性。HGG 似乎与其他癌症不同，可能是由于亚克隆与克隆新生抗原的普遍存在，这些抗原无法通过 ICI 引发免疫反应。本综述的主要目的是总结 HGG 中高度突变的现有知识，重点关注肿瘤突变负担和错配修复缺陷作为对 ICI 反应的潜在生物标志物的失败承诺。
