Lympho-myeloid aggregate-infiltrating CD20+ B cells display a double-negative phenotype and correlate with poor prognosis in esophageal squamous cell carcinoma

Nov 13, 2024Translational research : the journal of laboratory and clinical medicine

Special B cells with unusual features in immune cell clusters link to worse outcomes in esophageal cancer

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Abstract

In a study of 147 esophageal squamous cell carcinoma samples, lympho-myeloid aggregates were associated with poor prognosis.

Tumor-infiltrating B cells can be categorized into lympho-myeloid aggregates (LMAs) and tertiary lymphoid structures (TLSs).
LMAs were found to be widely distributed and their presence, particularly in the intra-tumor subregion, correlated with worse survival outcomes.
In contrast, TLSs exhibited a positive clinical significance for patients.
A four-level immune type based on the counts of LMAs and TLSs was identified as an independent predictor of survival.
The predominant B cell phenotype in LMAs was identified as double-negative B cells, which were associated with reduced overall survival.
Double-negative B cells showed a close relationship with regulatory T cells and expressed genes related to antigen processing and presentation.

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According to morphological features, tumor-infiltrating B cells (TIL-Bs) can be classified as lympho-myeloid aggregates (LMAs) and tertiary lymphoid structures (TLSs). As a disease with high incidence and mortality, research on esophageal squamous cell carcinoma (ESCC) TIL-Bs is still unclear. Thus, we aimed to investigate the prognostic value and functional involvement of TIL-Bs in ESCC. Based on CD20 immunohistochemical staining of 147 ESCC samples, the TIL-Bs at different anatomic subregions (intra-tumor (T), invasive margin (IM) and peri-tumor (P)) were quantified and correlated with survival by Kaplan-Meier analyses. We found that LMAs were widely distributed throughout the whole section and were associated with poor prognosis, especially those located in the T subregion, which was contrary to the positive clinical significance of TLSs. Based on the number of LMAs and TLSs, a four-level immune type was constructed as an independent predictor for survival. Using multiplexed immunofluorescence (mIF) staining, we found that the main phenotype of infiltrating B cells in LMAs was CD20IgDCD27double-negative (DN) B cells. DN B cells were abundant in ESCC tumor tissue, and their high expression was related to shortened overall survival time. Subsequently, we demonstrate a close relationship between DN B cells and regulatory T cells (Tregs) using single cell RNA-seq data, bulk RNA-seq data and flow cytometry, and verified the spatial proximity of DN B cells and Tregs by mIF staining. Trajectory analysis and flow cytometry revealed that DN B cells highly expressed genes involved in the antigen processing and presentation pathway, such as HLA-DR. The abundance of DN B cells and LMAs in ESCC provides novel potential targets for optimal immunotherapy against ESCC. + --

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Lympho-myeloid aggregate-infiltrating CD20+ B cells display a double-negative phenotype and correlate with poor prognosis in esophageal squamous cell carcinoma

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