Single-cell RNA-sequencing of immune cells (CD45+) from the tumor microenvironment. Single-cell RNA-sequencing of immune cells (CD45+) from the tumor microenvironment

In mouse models of PDGF-driven glioma where Notch is tumor-suppressive, we find that Notch activity shapes interferon-response in tumor cells and the local immune microenvironment early during tumor progression. Notch inhibition disturbs cytokine expression by tumor cells, altering recruitment and activation of immune cell populations and favoring hyper-proliferative "immune niche" independent growth. Genetic inactivation of Notch in glioma cells also attenuates their response to interferon-gamma establishing a non-cell autonomous inhibitory feedback loop that further promotes immune evasion and aggressiveness. Hence, we propose that Notch signaling levels in tumor cells are key to orchestrate immune escape and microenvironment independency during brain tumor formation. Overall design: CD45+ immune cells from pools of 9 healthy brains, 15 control tumors and 9 Rbpj-/- tumors were purified by FACS and analyzed by single cell RNA-seq.