Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas

作者：Enrique Blanco-Carmona, Ashwin Narayanan, Inmaculada Hernández, Juan C. Nieto, Marc Elosúa-Bayes, Xueyuan Sun, Claudia Schmidt, M. Necmettin Pamir, Koray Özduman, Christel Herold‐Mende, Francesca Pagani, Manuela Cominelli, Julián Taranda, Wolfgang Wick, Andreas von Deimling, Pietro Luigi Poliani, Michael Rehli, Matthias Schlesner, Holger Heyn, Şevin Turcan · 发表于：Cell Reports Medicine · 年份：2023 · DOI：10.1016/j.xcrm.2023.101249 · 被引用次数：35 · 研究领域：Glioma Diagnosis and Treatment、Neuroinflammation and Neurodegeneration Mechanisms、Immune cells in cancer

The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA and ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition to astrocyte-like, oligodendrocyte progenitor-like, and cycling tumor subpopulations, a tumor population enriched for ribosomal genes and translation elongation factors is primarily present in oligodendrogliomas. Longitudinal analysis of astrocytomas indicates that the proportion of tumor subpopulations remains stable in recurrent tumors. Analysis of tumor-associated microglia/macrophages (TAMs) reveals significant differences between oligodendrogliomas, with astrocytomas harboring inflammatory TAMs expressing phosphorylated STAT1, as confirmed by immunohistochemistry. Furthermore, inferred receptor-ligand interactions between tumor subpopulations and TAMs may contribute to TAM state diversity. Overall, our study sheds light on distinct tumor populations, TAM heterogeneity, TAM-tumor interactions in IDH-mutant glioma subtypes, and the relative stability of tumor subpopulations in recurrent astrocytomas.