Chen, JianTan, YunSun, FenghuanHou, LikunZhang, ChiGe, TaoYu, HuanshaWu, ChunxiaoZhu, YumingDuan, LiangWu, LiangSong, NanZhang, LipingZhang, WeiWang, DiChen, ChangWu, ChunyanJiang, GeningZhang, Peng2020-11-092020-11-092020-06-24Chen, J., Tan, Y., Sun, F., Hou, L., Zhang, C., Ge, T., Yu, H., Wu, C., Zhu, Y., Duan, L., Wu, L., Song, N., Zhang, L., Zhang, W., Wang, D., Chen, C., Wu, C., Jiang, G., & Zhang, P. (2020). Single-cell transcriptome and antigen-immunoglobin analysis reveals the diversity of B cells in non-small cell lung cancer. Genome Biology, 21(1), 152. https://doi.org/10.1186/s13059-020-02064-61474-760Xhttps://hdl.handle.net/1805/24329Background 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.en-USAttribution 4.0 Internationalnon-small cell lung cancerantigen-immunoglobin analysisSingle-cell transcriptomeB cellsArticle