Single‐cell transcriptome analysis reveals functional changes in tumour‐infiltrating B lymphocytes after chemotherapy in oesophageal squamous cell carcinoma

Abstract

Background Tumour immune microenvironment is related with carcinogenesis and efficacy of immunotherapy. B cells play major roles in humoral immunity, but detailed functions of tumour‐infiltrating B lymphocytes (TIL‐Bs) are unknown. Therefore, our aim was to investigate the functional heterogeneity of TIL‐Bs in oesophageal squamous cell carcinoma (ESCC) and lymph nodes (LNs) during chemotherapy. Methods Single‐cell transcriptome analysis was performed on 23 specimens. We also performed immunohistochemical analysis of immunoglobulin κ C (IGKC), an antibody‐secreting cell (ASC) marker, in 166 ESCC samples and evaluated the implication of IGKC in 2‐year recurrence free survival (RFS) and 3‐year overall survival (OS). Results A total of 81,246 cells were grouped into 24 clusters. We extracted B cell clusters based on canonical markers and identified 12 TIL‐B subtypes in ESCC. We found that several functions, such as co‐stimulation and CD40 signalling, were enhanced in TIL‐Bs after chemotherapy. The proportion of naive B cells (NBCs) decreased and B cell activation genes were up‐regulated in NBCs after chemotherapy. The proportion of ASCs in tumours increased with the loss of migratory abilities and antibody production in ASCs was promoted after chemotherapy. Differentially expressed genes up‐regulated with chemotherapy in ASCs correlated with prolonged survival with oesophageal cancer ( p = .028). In a metastatic LN, the ASC proportion increased and B cell differentiation was enhanced. In immunohistochemical analysis, RFS and OS of high IGKC expression cases were significantly better than those of low IGKC expression cases (RFS: p < .0001, OS: p < .0001). And in multivariable analysis, the expression of IGKC was an independent favourable prognostic factor for RFS (hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.12–0.45, p < .0001) and OS (HR: 0.20, 95% CI: 0.086–0.47, p = .0002) in ESCC. Conclusions Our findings provide novel insights for the heterogeneity of TIL‐Bs during chemotherapy and will be useful to understand the clinical importance of TIL‐Bs.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

“…T lymphocytes may recognize and bind the TAA peptides presented by major histocompatibility complex (MHC) molecules on tumor cells through the T-cell receptor, thereby initiating an immune response and triggering an attack on tumor cells[ 21 ]. In addition, natural killer (NK) lymphocytes and B lymphocytes play important roles in the regulation of immunoreactivity in EC[ 22 , 23 ]. For example, as a class of TAAs associated with 276 genes in more than 70 gene families, the antigen families formed by cancer-testis antigens (CTAs) are expressed mainly in ovarian granulosa cells and testicular germ cells, and are barely expressed in normal tissues[ 24 - 26 ].…”

The Novel-B-Cell-Related Gene Signature Predicts the Prognosis and Immune Status of Patients with Esophageal Carcinoma

“…However, investigations into the immune microenvironment of ESCA have predominantly focused on T cell functionality. In comparison, B cells, the second most prevalent immune cell type, have received relatively less attention in previous research 17 . Therefore, it is essential to gain a comprehensive understanding of the roles played by B cells within the ESCA microenvironment to comprehend the intricate interactions among distinct immunosubtypes, potentially leading to the discovery of innovative therapeutic strategies.…”

Identification of prognostic risk model based on plasma cell markers in hepatocellular carcinoma through single-cell sequencing analysis

“…TIL-Bs are increasingly recognized as pivotal players in modulating tumor responses, thereby making them promising targets for therapeutic interventions ( Yuen et al, 2016 ). However, the heterogeneity of TIL-Bs determines their dual role in anti-tumor immunity ( Laumont et al, 2022 ; Nakamura et al, 2023 ). TIL-Bs actively participate in cellular immunity by engaging in antigen presentation and fostering the development of tertiary lymphoid structures (TLS).…”