The interplay between immune cells and tumor cells determines the fate of tumorigenesis. Targeting the abnormal immune response of tumors has been recently achieved great success in some patients. Emerging evidence demonstrated the nervous system plays vital roles in immune regulation, but if the nervous system affects the immune-tumor response and the possible mechanism involved remain largely unexplored. Here, we report that Schwann cells, the major component of the peripheral nervous system (PNS), induce M2 polarization of macrophages by secreting cytokines and chemokines, and these polarized macrophages promote the proliferation of lung cancer cells. We cocultured peripheral blood mononuclear cells (PBMCs) with Schwann cells or treated PBMCs with the culture supernatant of Schwann cells. We found that both treatments induced M2 polarization of the macrophages in peripheral blood mononuclear cell cultures. We performed a bioinformatic analysis of the transcriptome of Schwann cells and analyzed cytokines and chemokines by ELISAs. We found that Schwann cells secreted high levels of CCL2, CXCL5, CXCL12, and CXCL8. CCL2 promotes the M2 polarization of macrophages. Furthermore, we isolated CD14-positive macrophages that were cocultured with the Schwann cells and treated A549 and H1299 lung cancer cells with these macrophages. We found that the Schwann cell-polarized macrophages increased the proliferation of the lung cancer cells. Our study sheds new light on the involvement of the PNS in the regulation of tumor progression via a “Schwann cell”-“immune cell”-“tumor cell” axis.

免疫细胞与肿瘤细胞之间的相互作用决定了肿瘤发生的命运。最近，在某些患者中靶向肿瘤的异常免疫反应已获得巨大成功。越来越多的证据表明，神经系统在免疫调节中起着至关重要的作用，但是如果神经系统影响免疫肿瘤反应，并且可能的机制尚不清楚。在这里，我们报道，周围神经系统（PNS）的主要成分雪旺细胞通过分泌细胞因子和趋化因子诱导巨噬细胞的M2极化，而这些极化的巨噬细胞促进了肺癌细胞的增殖。我们与雪旺氏细胞共培养外周血单核细胞（PBMC）或与雪旺氏细胞的培养上清液一起处理PBMC。我们发现这两种治疗方法都可诱导外周血单核细胞培养物中巨噬细胞的M2极化。我们对雪旺氏细胞的转录组进行了生物信息学分析，并通过ELISA分析了细胞因子和趋化因子。我们发现雪旺细胞分泌高水平的CCL2，CXCL5，CXCL12和CXCL8。CCL2促进巨噬细胞的M2极化。此外，我们分离了与雪旺氏细胞共培养的CD14阳性巨噬细胞，并用这些巨噬细胞处理了A549和H1299肺癌细胞。我们发现，施旺细胞极化的巨噬细胞增加了肺癌细胞的增殖。我们的研究为PNS通过“ Schwann细胞”-“免疫细胞”-“肿瘤细胞”轴参与肿瘤进展的调控提供了新的思路。