The role of tumor-infiltrating B cells in the tumor microenvironment of hepatocellular carcinoma and its prognostic value: a bioinformatics analysis

Journal of Gastrointestinal Oncology

article

Jixue Zou¹  Chubin Luo³  Haoyang Xin³  Tongchun Xue¹  Xiaoying Xie¹  Rongxin Chen¹  Lan Zhang¹ 

[1] Liver Cancer Institute, Zhongshan Hospital, Fudan University;National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University;Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University;Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education

关键词: Hepatocellular carcinoma (HCC);    tumor microenvironment (TME);    B cells;    prognosis;   

DOI  :  10.21037/jgo-22-717

学科分类：肿瘤学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: Accumulating evidence indicates that tumor heterogeneity is characterized by distinct immunosubtypes. However, prior studies have mainly focused on the functions of T cells. The role of tumor-infiltrating B cells in the microenvironment of hepatocellular carcinoma (HCC) requires further investigation. Methods: We conducted an integrative analysis of single cell RNA sequencing (scRNA-seq) datasets in HCC tumor samples from Gene Expression Omnibus database. We analyzed the features of B cells in normal liver tissue and HCC. Additionally, we conducted a deconvolution analysis using the matrix of scRNA-seq datasets and the RNA-seq datasets in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database. The survival analyses of the TCGA-LIHC cohort with different B cell infiltration rates and was further validated. Finally, we performed immunohistochemistry analysis of primary tumor tissue of HCC patients using antibodies against CD79A and validated the impact of tumor-infiltrating B cells in the prognosis of LIHC. Results: We identified several subtypes of B cells in the microenvironment of HCC, including the plasma cells and naïve B cells. The relative ratio of B cells, but not the plasma cells, was significantly decreased in HCC as compared to the normal liver tissue (P<0.05). In addition, genes related to antigen presentation and cell proliferation were decreased in tumor-infiltrating B cells (P<0.05). The observation of B cell infiltration was further validated with the TCGA-LIHC cohort. The overall survival and disease-free survival in HCC patients with higher B-cell infiltration rate were significantly longer than those in the lower infiltration group (P<0.05) in the TCGA-LIHC cohort. Moreover, we demonstrated higher infiltration rates of B cells were significantly associated with a better prognosis of HCC in our cohort. Conclusions: Tumor-infiltrating B cells potentially exert a tumor-suppressive function in the microenvironment of HCC and the higher levels of B cell infiltration are associated with a favorable outcome of HCC. Targeted activation of B cells may improve the tumor immune-targeted therapy.

【 授权许可】

Unknown