Integrative Molecular and Immune Characterization of FCGR2B in Glioma

Background: Currently, there are no immunotherapeutic management approaches that show satisfactory survival benefits in glioma patients. Recent studies reported the functions of Fc gamma receptors in anti-CLTA4 and anti-PD1 treatment, with FCGR2B as a critical checkpoint in B cell mediated immune responses. However, the function of FCGR2B in glioma development remains unknown. In the current study, we sought to figure out the molecular and clinical characterization of FCGR2B in glioma. Method and Patients: A total of 320 and 697 glioma RNA-seq data were obtained from CGGA and TCGA databases respectively for our analysis. We also analyzed single-cell RNA sequence data (scRNA-seq) to characterize cell heterogeneity in the tumors. Immunohistochemistry (IHC) was used to assess FCGR2B expression as well as its the association with other identified checkpoints at the protein level. We performed all statistical analyses and generation of graphs using the R language. Results: We found upregulation of FCGR2B in glioblastoma, especially in cases with mesenchymal subtype, and isocitrate dehydrogenase (IDH) wild-type patients. Samples with IDH mutation tended to enrich in FCGR2B low expression group. Gene ontology and cell lineage analysis revealed a strong association between FCGR2B with T- cell, macrophages, and neutrophils mediated immune activities, with subsequent involvement in inflammation responses. Higher FCGR2B expression was associated with more infiltrating immune and stromal cells. Furthermore, FCGR2B was positively correlated with genes encoding some critical checkpoints including CTLA-4, PD1/PDL1 as well as its homologs, FCGR2A and FCGR2B. Finally, we identified that FCGR2B expression was an independent survival predictor using cox analysis and established a nomogram model combining with other clinical factors. Conclusion: FCGR2B is crucial in establishing glioma immune-resistant milieu. Targeting FCGR2B may improve the therapeutic efficacy of current checkpoint inhibitors in glioma. Funding Statement: This work was supported by the National Natural Science Foundation of China (NO.81703622),China Postdoctoral Science Foundation (NO. 2018M633002), Hunan Provincial Natural Science Foundation of China (NO.2018JJ3838). Declaration of Interests: The authors declare no conflict of interests. Ethics Approval Statement: Our research strategy was approved by the Research Ethics Committee of the Xiangya Hospital of Central South University (No. 2017121019) with written informed consent obtained from all patients before inclusion in the study.