LANDSCAPE ANALYSIS OF SINGLE-CELL RNA SEQUENCING IN FcγRIIB DEFICIENCY AGAINST BRAIN CANCER

Abstract

Glioblastoma (GBM) is a deadly cancer in the central nervous system, and standard treatments show limited success. Immune checkpoint inhibitors (ICIs) have shown promise in treating hematological cancers, but their application in GBM patients has been limited due to a lack of understanding of the tumor microenvironment (TME). This study used single-cell RNA sequencing analysis to investigate the role of tumor-infiltrating immune cells in GBM and found that the inhibitory FcγRIIB gene was upregulated in tumor-infiltrating immune cells, suppressing the antitumor response. FcγRIIB plays a crucial role in immune homeostasis, and its blocking or deletion leads to a proinflammatory response. We used FcγRIIB-KO mice to investigate its function in GBM, and found that at the early stages of GBM (10 days), the tumor-associated microglia were polarized from a pro- to an anti-tumoral state. The microglia enhanced the TNF-alpha signaling pathway and upregulated adaptive immune cell recruiting chemokines such as Ccl3 and Ccl4. Furthermore, the tumor-infiltrating lymphocytes, particularly CD8 T cells, showed an enriched precursor of exhausted T cell gene signature. At the later stages of tumor progression (20 days), the total number of immune cells increased in FcγRIIB-KO mice, with an increase in cytotoxic CD8 T cells infiltrating the tumor site and an enhanced cytotoxicity with enriched gene expression of Prf1 and Gzmb. Our findings indicate that FcγRIIB plays critical roles in GBM infiltrating immune cells, particularly microglia and cytotoxic CD8 T cells. Our study provides a comprehensive dataset on the heterogeneity of GBM-associated immune cells, shedding light on the role of FcγRIIB in GBM. .