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

肿瘤微环境中的生发中心B细胞亚群不容忽视:它们与头颈部鳞状细胞癌的预后、免疫治疗反应和治疗耐药性密切相关。

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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: naive B cells (NBs), germinal center B cells (GCBs), memory B cells (MBs), and plasma cells (PCs). 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. Cellular communication revealed that GCBs acted on tumor cells through the CD99 and SEMA4 signaling pathways. The independent prognostic value, immune cell infiltration, TMB and drug sensitivity assays were validated for the MEF2B(+) GCB score groups. CONCLUSIONS: We identified GCBs as B cell-specific prognostic biomarkers for the first time. 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.

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