Redefining the immune microenvironment of gliomas in the era of single-cell genomics

Infiltrating gliomas are the most common primary malignant brain tumor and remain universally fatal. Over the past decade, advances in single-cell technologies, including single-cell RNA sequencing, have significantly advanced our understanding of malignant cells in glioma. These efforts have revealed extensive transcriptional heterogeneity and plasticity within glioma cells, identifying distinct cellular states and developmental programs that are discussed elsewhere. Recognizing that the tumor microenvironment constitutes sometimes more than half of the cells in gliomas, and that it has a profound impact on glioma cellular states, recent research has focused on non-malignant cells and their interactions with cancer cells. The present review reflects on lessons learned from single-cell genomics on the tumor immune microenvironment (TIME) of gliomas, as the dominant component of the tumor outside of the malignant cells and explores implications for developing effective immunotherapies.