biostudies-literatureDang MTAlex's Lemonade Stand Foundation for Childhood CancerBurroughs Wellcome FundNIAID NIH HHSNCI NIH HHSNINDS NIH HHSNational Institutes of Health108917https://www.ebi.ac.uk/biostudies/studies/S-EPMC10450591biostudies-literatureUnknown34(13)Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation. Our analyses reveal significant TAM heterogeneity, identify markers of ontologically distinct TAM subsets, and show the impact of brain microenvironment on the differentiation of tumor-infiltrating moCell reportsMacrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality.PMC10450591L40 CA189113K12 NS098482T32 NS007413K08 AI106953Folkert IWGreene CSArif SHaldar MDevalaraja SRaman PTaroni JNTo TKJYoung PHakonarson HCurran TZhai LDang MTRathi KSGaonkar KSAlam ZShapiro JASavonen CMartinez DGonzalez MVRokita JLMafra FfalseMacrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality.Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation. Our analyses reveal significant TAM heterogeneity, identify markers of ontologically distinct TAM subsets, and show the impact of brain microenvironment on the differentiation of tumor-infiltrating mo2021-01-01T00:00:00Z2021 Mar2026-05-28T12:17:11.492Z2025-04-07T10:22:41.468ZS-EPMC104505913378911310.1016/j.celrep.2021.108917