Single-cell landscape analysis of tumor infiltrated immune cell population in FcγRIIB deficiency against glioblastoma

Abstract

Glioblastoma (GBM) is the most common and deadliest cancer known in the central nervous system. Immune checkpoint inhibitors (ICIs) are effective in clinical trials for hematological tumors. However, the application of ICIs is for GBM patients has not proven to be completely successful. The limitations of the treatments can be attributed to the lack of an understanding of the GBM microenvironment (TME), which consists of heterogeneous tumor stem cells and various types of immune cells. Thus, investigating these tumor-infiltrating immune cells and their functions can provide a better insight to the TME of GBM. In order to accomplish this, we performed single-cell RNA sequencing analysis using the GBM mouse model. From the results, the TME up-regulated the inhibitory FcγR gene, Fcgr2b, on infiltrating immune cells, and this inhibitory receptor suppressed the antitumor immune response against GBM. FcγRIIB is known to mediate immune homeostasis through the binding of the immune complex, and blocking the receptor induces a proinflammatory response. We were able to use the FcγRIIB knockout mouse (KO) and analyze the landscape of tumor-infiltrating immune cells. Tumor-associated microglia portrayed anti-tumoral characteristics in KO mice and we were able to see an upregulation of adaptive immune cell recruiting chemokines. In addition, CD8 T cells showed an enrichment of precursor genes related to T cell exhaustion. With tumor progression, the total immune cell number had increased in KO mouse and CD8 T cells enhanced cytotoxic related genes. We can interpret from these results that FcγRIIB plays a critical role in GBM infiltrating immune cells, and targeting of this receptor could be a possible treatment option for treatment of GBM.