biostudies-literatureAndrade AFNICHD NIH HHSNCATS NIH HHSNIAID NIH HHSNCI NIH HHS7769https://www.ebi.ac.uk/biostudies/studies/S-EPMC11377583biostudies-literatureUnknown15(1)Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), particularly the immune infiltrate. Here, we characterize the immune TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic, proteomic and spatial single-cell approaches. Resolution of immune lineages indicates high infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoint markers, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M mouse models tested. We show these myeloid populations communicate with H3-mutant cells, mediatNature communicationsImmune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function.PMC11377583R21 TR002639P01 CA196539R01 AI171980R21 HD102565Pathania MAndrade AFKrug BMcNicholas MFaury DWeil AGTopouza DGWu QJessa SZeinieh MDudley RWRWalsh LAWei YLiu YChandarana BQuail DFKleinman CLPuligandla EEllezam BKarimi EJabado NRezanejad MRusso CKaramchandani JLlivichuzhca-Loja DDe Cola AAnnett ALarouche VNakada EMKonnikova LGehlhaar AJuretic NGonzalez Santiago EGHebert SAgnihotri SDanieau GfalseImmune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function.Histone H3-mutant gliomas are deadly brain tumors characterized by a dysregulated epigenome and stalled differentiation. In contrast to the extensive datasets available on tumor cells, limited information exists on their tumor microenvironment (TME), particularly the immune infiltrate. Here, we characterize the immune TME of H3.3K27M and G34R/V-mutant gliomas, and multiple H3.3K27M mouse models, using transcriptomic, proteomic and spatial single-cell approaches. Resolution of immune lineages indicates high infiltration of H3-mutant gliomas with diverse myeloid populations, high-level expression of immune checkpoint markers, and scarce lymphoid cells, findings uniformly reproduced in all H3.3K27M mouse models tested. We show these myeloid populations communicate with H3-mutant cells, mediat2024-01-01T00:00:00Z2024 Sep2026-07-15T13:00:33.891Z2025-04-05T14:38:41.14ZS-EPMC113775833923751510.1038/s41467-024-52096-w