%0 Journal Article
%A Ahmad, Olfat
%A Ahmad, Tahani
%A Pfister, Stefan
%T IDH mutation, glioma immunogenicity, and therapeutic challenge of primary mismatch repair deficient IDH-mutant astrocytoma PMMRDIA: a systematic review.
%J Molecular oncology
%V 18
%N 12
%@ 1574-7891
%C Hoboken, NJ
%I John Wiley & Sons, Inc.
%M DKFZ-2024-00326
%P 2822-2841
%D 2024
%Z 2024 Dec;18(12):2822-2841 / #EA:B062#LA:B062#
%X In 2021, Suwala et al. described Primary Mismatch Repair Deficient IDH-mutant Astrocytoma (PMMRDIA) as a distinct group of gliomas. In unsupervised clustering, PMMRDIA forms distinct cluster, separate from other IDH-mutant gliomas, including IDH-mutant gliomas with secondary mismatch repair (MMR) deficiency. In the published cohort, three patients received treatment with an immune checkpoint blocker (ICB), yet none exhibited a response, which aligns with existing knowledge about the decreased immunogenicity of IDH-mutant gliomas in comparison to IDH-wildtype. In the case of PMMRDIA, the inherent resistance to the standard-of-care temozolomide caused by MMR deficiency is an additional challenge. It is known that a gain-of-function mutation of IDH1/2 genes produces the oncometabolite R-2-hydroxyglutarate (R-2-HG), which increases DNA and histone methylation contributing to the characteristic glioma-associated CpG island methylator phenotype (G-CIMP). While other factors could be involved in remodeling the tumor microenvironment (TME) of IDH-mutant gliomas, this systematic review emphasizes the role of R-2-HG and the subsequent G-CIMP in immune suppression. This highlights a potential actionable pathway to enhance the response of ICB, which might be relevant for addressing the unmet therapeutic challenge of PMMRDIA.
%K IDH-mutant glioma (Other)
%K PMMRDIA (Other)
%K immunogenicity (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38339779
%R 10.1002/1878-0261.13598
%U https://inrepo02.dkfz.de/record/288068