Macrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality

• DOI: 10.1016/j.celrep.2021.108917
• Publication Date: 2021-03-31T00:56:08Z
• Authors: Mai T. Dang; Michael V. Gonzalez; Krutika S. Gaonkar; Komal S. Rathi; Patricia Young; Sherjeel Arif; Li Zhai; Zahidul Alam; Samir Devalaraja; Tsun Ki Jerrick To; Ian W. Folkert; Pichai Raman; Jo Lynne Rokita; Daniel Martinez; Jaclyn N. Taroni; Joshua A. Shapiro; Casey S. Greene; Candace Savonen; Fernanda Mafra; Hakon Hakonarson; Tom Curran; Malay Haldar
• Keywords: Genetic Markers; 0301 basic medicine; Transcription, Genetic; QH301-705.5; Macrophages; CD8-Positive T-Lymphocytes; Article; Monocytes; 3. Good health; Mice; 03 medical and health sciences; Tumor Microenvironment; Animals; Humans; Hedgehog Proteins; Microglia; Biology (General); Single-Cell Analysis; Cerebellar Neoplasms; Medulloblastoma

Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, ontology. Transcriptomic analyses human medulloblastoma, the most common malignant pediatric brain cancer, showed medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated by single-cell RNA sequencing autochthonous murine SHH-MB at steady state under two treatment modalities: molecular-targeted inhibitor radiation. Our reveal significant TAM heterogeneity, identify markers ontologically subsets, show impact microenvironment on differentiation tumor-infiltrating monocytes. composition undergoes dramatic changes differs between radiation therapy. We immunosuppressive monocyte-derived subset emerges therapy demonstrate its regulating T cell neutrophil infiltration MB.