• Qing-Feng Huang, Ge-Fei Wang, Yi-Meng Zhang, Cong Zhang, Ying-Qi Ran, Jian-Zhong He, Geng Wang, Xiu-E Xu, Shao-Hong Wang, Jian-Yi Wu, En-Min Li, and Li-Yan Xu.
• Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, PR China; Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, PR China.
• Transl Res. 2025 Jan 1; 275: 486148-61.

AbstractAccording 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 CD20+IgD-CD27- double-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.Copyright © 2024. Published by Elsevier Inc.

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