Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Int J Cancer. 2019 Aug 15;145(4):1099-1110. doi: 10.1002/ijc.32151. Epub 2019 Feb 7.
Tumor-associated macrophages (TAMs), key immune cells in the tumor microenvironment, are shown to be closely correlated with the progression of non-small cell lung cancer (NSCLC). Cancer stem cells (CSCs) can contribute to NSCLC progression as well. We aimed to clarify whether TAMs promote the progression of NSCLC by mainly affecting the activities of CSCs. We found that TAM-like cells promoted CSC-like properties in NSCLC cells in vitro, which was mediated by TAM-derived IL-10. TAM-derived IL-10 promoted CSC-like properties of NSCLC cells through JAK1/STAT1/NF-κB/Notch1 signaling. Blockade of IL-10/JAK1 signaling inhibited TAM-mediated NSCLC tumor growth in vivo, and the TAM-mediated expression of CSC-related and mesenchymal-related genes in NSCLC. Lastly, expression levels of these signaling molecules were significantly correlated with survival of NSCLC patients. Therefore, IL-10/JAK1 signaling might be a potential therapeutic target for NSCLC treatment.
肿瘤相关巨噬细胞（TAMs）是肿瘤微环境中的关键免疫细胞，与非小细胞肺癌（NSCLC）的进展密切相关。癌症干细胞（CSCs）也可以促进 NSCLC 的进展。我们旨在阐明 TAMs 是否主要通过影响 CSCs 的活性来促进 NSCLC 的进展。我们发现 TAM 样细胞在体外促进 NSCLC 细胞的 CSC 样特性，这是由 TAM 衍生的 IL-10 介导的。TAM 衍生的 IL-10 通过 JAK1/STAT1/NF-κB/Notch1 信号促进 NSCLC 细胞的 CSC 样特性。阻断 IL-10/JAK1 信号可抑制体内 TAM 介导的 NSCLC 肿瘤生长，以及 TAM 介导的 NSCLC 中与 CSC 相关和间充质相关基因的表达。最后，这些信号分子的表达水平与 NSCLC 患者的生存显著相关。因此，IL-10/JAK1 信号可能是 NSCLC 治疗的潜在治疗靶点。
Zotero 插件