Single-cell transcriptome and antigen-immunoglobin analysis reveals the diversity of B cells in non-small cell lung cancer
Posted on 2020-06-25 - 03:35
Abstract 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.
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Chen, Jian; Tan, Yun; Sun, Fenghuan; Hou, Likun; Zhang, Chi; Ge, Tao; et al. (2020). Single-cell transcriptome and antigen-immunoglobin analysis reveals the diversity of B cells in non-small cell lung cancer. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5038241.v1
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AUTHORS (19)
JC
Jian Chen
YT
Yun Tan
FS
Fenghuan Sun
LH
Likun Hou
CZ
Chi Zhang
TG
Tao Ge
HY
Huansha Yu
CW
Chunxiao Wu
YZ
Yuming Zhu
LD
Liang Duan
LW
Liang Wu
NS
Nan Song
LZ
Liping Zhang
WZ
Wei Zhang
DW
Di Wang
CC
Chang Chen
CW
Chunyan Wu
GJ
Gening Jiang
PZ
Peng Zhang
KEYWORDS
non-small cell lung cancerNSCLCB cellscancer cell growthtumor-infiltrating B cellsïve B cellsnon-small cell lung cancer Abstract Background Malignant transformationTMEtumor tissue samplesdysregulated tumor microenvironmentlung cancer cellsplasma-like B celllung cancer cell linescell growthplasma-like B cellscell typestumor-infiltrated B cells