Single-Cell Transcriptomic Profile Reveals Macrophage Heterogeneity in Medulloblastoma and Their Treatment-Dependent Recruitment
Mai T. Dang, Michael Gonzalez, Krutika S. Gaonkar, Komal S. Rathi, Patricia Young, Sherjeel Arif, Li Zhai, Md Zahidul Alam, Samir Devalaraja, Tsun Ki To, Ian W. Folkert, Pichai Ramen, Jo Lynne Rokita, Daniel Martinez, Jaclyn N. Taroni, Joshua Shapiro, Casey S. Greene, Candace Savonen, Hakon Hakonarson, Tom Curran, Malay Haldar
Abstract
The role of macrophages in medulloblastoma, the most common malignant pediatric brain tumor, is unclear. Using single-cell RNA sequencing in a mouse model of sonic hedgehog medulloblastoma and analysis of bulk RNA sequencing of human medulloblastoma, we investigated macrophage heterogeneity. Our findings reveal differential recruitment of macrophages with molecular-targeted versus radiation therapy and identify an immunosuppressive monocyte-derived macrophages following radiation treatment of mouse medulloblastoma, uncovering potential strategies for immunomodulation as adjunctive therapy.