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.

中文翻译：

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单细胞转录组和抗原免疫球蛋白分析揭示非小细胞肺癌中 B 细胞的多样性

背景 癌症的恶性转化和进展是由癌细胞及其失调的肿瘤微环境 (TME) 共同进化驱动的。最近关于免疫疗法的研究证明了恢复 T 细胞抗肿瘤功能的功效，突出了靶向 TME 中某些细胞类型的治疗潜力。然而，其他免疫细胞类型的功能在很大程度上仍未得到探索。结果我们对从非小细胞肺癌 (NSCLC) 患者的肿瘤组织样本中分离的细胞进行了单细胞 RNA-seq 分析，并确定了肿瘤浸润 B 细胞的亚型及其在 NSCLC 进展中的多种功能。两个独立队列的流式细胞术和免疫组织化学实验证实了 B 细胞的两种主要亚型共存，即幼稚样和血浆样 B 细胞。晚期 NSCLC 中幼稚样 B 细胞减少，其水平较低与预后不良有关。来自 NSCLC 患者的分离的幼稚样 B 细胞与两种肺癌细胞系的共培养表明幼稚样 B 细胞通过分泌四种负调节细胞生长的因子来抑制肺癌细胞的生长。我们还证明血浆样 B 细胞在 NSCLC 早期抑制癌细胞生长，但在 NSCLC 晚期促进细胞生长。蛋白质组学数据进一步验证了血浆样 B 细胞产生的免疫球蛋白及其相互作用蛋白在 NSCLC 进展中的作用。结论我们的分析揭示了肿瘤浸润 B 细胞的多种功能及其在 NSCLC 中的潜在临床意义。