Journal Article

Single-cell transcriptome and antigen-immunoglobin analysis reveals the diversity of B cells in non-small cell lung cancer

Jiang, Gening, Zhang, Peng, Sun, Fenghuan, Zhang, Wei, Wu, Chunyan, Duan, Liang, Chen, Jian, Wang, Di, Song, Nan, Chen, Chang, Tan, Yun, Zhu, Yuming, Zhang, Liping, Hou, Likun, Yu, Huansha, Wu, Liang, Zhang, Chi, Wu, Chunxiao, Ge, Tao

2020

Overview

Background Malignant transformation and progression of cancer are driven by the co-evolution of cancer cells and their dysregulated tumor microenvironment (TME). Recent studies on immunotherapy demonstrate the efficacy in reverting the anti-tumoral function of T cells, highlighting the therapeutic potential in targeting certain cell types in TME. However, the functions of other immune cell types remain largely unexplored. Results We conduct a single-cell RNA-seq analysis of cells isolated from tumor tissue samples of non-small cell lung cancer (NSCLC) patients, and identify subtypes of tumor-infiltrated B cells and their diverse functions in the progression of NSCLC. Flow cytometry and immunohistochemistry experiments on two independent cohorts confirm the co-existence of the two major subtypes of B cells, namely the naïve-like and plasma-like B cells. The naïve-like B cells are decreased in advanced NSCLC, and their lower level is associated with poor prognosis. Co-culture of isolated naïve-like B cells from NSCLC patients with two lung cancer cell lines demonstrate that the naïve-like B cells suppress the growth of lung cancer cells by secreting four factors negatively regulating the cell growth. We also demonstrate that the plasma-like B cells inhibit cancer cell growth in the early stage of NSCLC, but promote cell growth in the advanced stage of NSCLC. The roles of the plasma-like B cell produced immunoglobulins, and their interacting proteins in the progression of NSCLC are further validated by proteomics data. Conclusion Our analysis reveals versatile functions of tumor-infiltrating B cells and their potential clinical implications in NSCLC.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Animal Genetics and Genomics / Antigens / B-lymphocytes / Bioinformatics / Biomedical and Life Sciences / Blood / Breast cancer / Cancer Evolution and Metastasis / Cell culture / cell growth / coculture / coevolution / Evolutionary Biology / Flow cytometry / Gene expression / genome / Genomics / Human Genetics / Immunoglobulins / Immunohistochemistry / Immunotherapy / Life Sciences / Lung cancer / lung neoplasms / Lymphocytes / Lymphocytes B / Lymphocytes T / Melanoma / Microbial Genetics and Genomics / neoplasm cells / Non-small cell lung carcinoma / Plant Genetics and Genomics / prognosis / Proteomics / Ribonucleic acid / RNA / sequence analysis / Small cell lung carcinoma / transcriptome / Tumor cell lines