Analysis of antitumor immunity in mouse glioma microenvironment through intercellular communication.

Objective: This study aimed to map the antitumor immunity in the glioma microenvironment by analyzing intercellular communication.

Materials And Methods: The single-cell RNA-sequencing (scRNA-Seq) data were obtained from fresh mouse gliomas. Tumor cells were inferred by estimating genomic copy number profiles. CellMarker database was used to identify cell types. Intercellular communication was inferred using CellChat. Flow cytometry was used to detect the effect of microglia or stroma-educated monocytes on CD4 T cell proliferation.

Results: Mouse glioma contained at least eight cell populations, and T cells were the only infiltrating immunocytes. Whether in signal outgoing or signal incoming, intercellular communication could be divided into four patterns by which cell populations in the tumor microenvironment (TME) cooperate with each other. By analyzing the complex communication between brain cell populations and infiltrating T cells in TME, we found that the brain cell populations used 25 signaling pathways to connect to T cells, and T cells used 21 signaling pathways to connect to brain cell populations. We also found that microglia from normal mice and brain stroma-educated monocytes exhibited immunosuppressive activity against CD4 T cell proliferation.

Conclusions: We described the previously underestimated complex communication between infiltrating T cells and brain cell populations. Our data suggest that the tolerogenic property of glioma TME is related to the immune privilege of CNS.