Germinal center B-cell subgroups in the tumor microenvironment cannot be overlooked: their involvement in prognosis, immunotherapy response, and treatment resistance in head and neck squamous carcinoma

Abstract

Abstract Background More than 60% of patients with head and neck squamous carcinoma (HNSCC) are diagnosed at advanced stages and miss radical treatment. This has prompted the need to find new biomarkers to achieve early diagnosis and predict early recurrence and metastasis of tumors. Methods Single-cell RNA sequencing (scRNA-seq) data from HNSCC tissues and peripheral blood samples were obtained through the Gene Expression Omnibus (GEO) database (GSE164690) to characterize the B-cell subgroups, differentiation trajectories, and intercellular communication networks in HNSCC and to construct a prognostic model of the associated risks. In addition, this study analyzed the differences in clinical features, immune cell infiltration, functional enrichment, tumor mutational burden (TMB), and drug sensitivity between the high- and low-risk groups. Results Using scRNA-seq of HNSCC, we classified B and plasma cells into a total of four subgroups for the first time: naive B cells (NBs), germinal center B cells (GCBs), memory B cells (MBs), and plasma cells (PCs) and analyzed each subgroup separately. Pseudotemporal trajectory analysis revealed that NBs and GCBs were at the early stage of B cell differentiation, while MBs and PCs were at the end stage. Cellular communication revealed that GCBs acted on tumor cells through the CD99 and SEMA4 signaling pathways. By employing univariate Cox regression, Lasso, and multivariate Cox regression analysis, we developed several risk scores based on marker genes of GCBs subgroups, especially the independent prognostic value of MEF2B+ GCB score was validated. The results of immune cell infiltration, TMB, and drug sensitivity assays were significantly different in HNSCC samples from high and low- MEF2B+ GCB score groups. Conclusions This study provides ideas to unravel the fundamental biological functions of B cells and their complex mechanistic roles. For the first time, we identified GCBs as B cell-specific prognostic biomarkers. The MEF2B+ GCB score fills the research gap in the genetic prognostic prediction model of HNSCC and is expected to provide a theoretical basis for finding new therapeutic targets for HNSCC.