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

Autor: Huang QF; 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., Wang GF; Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, PR China., Zhang YM; 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., Zhang C; 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., Ran YQ; 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., He JZ; Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, Guangdong Province, PR China., Wang G; Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, PR China., Xu XE; 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., Wang SH; Departments of Pathology, Shantou Central Hospital, Shantou 515041, Guangdong, PR China., Wu JY; 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., Li EM; 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; Shantou Academy Medical Sciences, Shantou 515041, Guangdong, PR China; Guangdong Esophageal Cancer Research Institute, Shantou Sub-center, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China. Electronic address: nmli@stu.edu.cn., Xu LY; 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; Guangdong Esophageal Cancer Research Institute, Shantou Sub-center, Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China. Electronic address: lyxu@stu.edu.cn.
Jazyk: angličtina
Zdroj: Translational research : the journal of laboratory and clinical medicine [Transl Res] 2025 Jan; Vol. 275, pp. 48-61. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1016/j.trsl.2024.11.002
Abstrakt: 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 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.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest and all authors have read the journal's authorship statement.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: