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

Blanco-Carmona, Enrique; Narayanan, Ashwin; Hernandez, Inmaculada; Nieto, Juan C.; Elosua-Bayés, Marc; Sun, Xueyuan; Schmidt, Claudia; Pamir, Necmettin; Özduman, Koray; Herold-Mende, Christel; Pagani, Francesca; Cominelli, Manuela; Taranda, Julian; Wick, Wolfgang; von Deimling, Andreas; Poliani, Pietro Luigi; Rehli, Michael; Schlesner, Matthias; Heyn, Holger; Turcan, Sevin

doi:http://dx.doi.org/10.1016/j.xcrm.2023.101249

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

Citació

Blanco-Carmona E, Narayanan A, Hernandez I, Nieto JC, Elosua-Bayes M, Sun X, Schmidt C, Pamir N, Özduman K, Herold-Mende C, Pagani F, Cominelli M, Taranda J, Wick W, von Deimling A, Poliani PL, Rehli M, Schlesner M, Heyn H, Turcan S. Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas. Cell Rep Med. 2023 Nov 21;4(11):101249. DOI: 10.1016/j.xcrm.2023.101249

Resum

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.