@article{d9397c8491fe43c886f4c6ff586e989c,
title = "IL-10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF-κB/Notch1 pathway in non-small cell lung cancer",
abstract = "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.",
keywords = "IL-10, cancer stem cells, non-small cell lung cancer, tumor microenvironment, tumor-associated macrophages",
author = "Li Yang and Ying Dong and Yanjun Li and Dong Wang and Shasha Liu and Dan Wang and Qun Gao and Shaofei Ji and Xinfeng Chen and Qingyang Lei and Wenyi Jiang and Liping Wang and Bin Zhang and Yu, {Jane J.} and Yi Zhang",
note = "Funding Information: Key words: non-small cell lung cancer, tumor microenvironment, cancer stem cells, tumor-associated macrophages, IL-10 Abbreviations: CSCs: cancer stem cells; EMT: epithelial-mesenchymal transition; IL-10RA: IL-10 receptor; MACS: magnetic cell sorting; NSCLC: non-small cell lung cancer; OS: overall survival; PBMs: peripheral blood monocytes; PFS: progression-free survival; TAMs: tumor-associated macrophages; TCGA: The Cancer Genome Atlas Additional Supporting Information may be found in the online version of this article. Conflict of interest: The authors declare no conflicts of interest. Grant sponsor: Ministry of Public Health; Grant number: 201501004; Grant sponsor: Science and Technology Department of Henan Province; Grant number: 162102410059; Grant sponsor: Research and Development; Grant number: 2016YFC1303501; Grant sponsor: National Natural Science Foundation of China; Grant numbers: 81602024, 81771781, 81872410 DOI: 10.1002/ijc.32151 History: Received 27 Sep 2018; Accepted 16 Jan 2019; Online 22 Jan 2019 Correspondence to: Dr. Yi Zhang, Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People{\textquoteright}s Republic of China, Tel.: +86-371-66295320, E-mail: yizhang@zzu.edu.cn Funding Information: This study was supported by grants from the National Natural Science Foundation of China (No.81771781, No.81602024, No.81872410), Funding from State's Key Project of Research and Development Plan (No. 2016YFC1303501), International Research Cooperation Grant from Science and Technology Department of Henan Province (No.162102410059), Research Grant from the Ministry of Public Health (No.201501004). Funding Information: This study was supported by grants from the National Natural Science Foundation of China (No.81771781, No.81602024, No.81872410), Funding from State{\textquoteright}s Key Project of Research and Development Plan (No. 2016YFC1303501), International Research Cooperation Grant from Science and Technology Department of Henan Province (No.162102410059), Research Grant from the Ministry of Public Health (No.201501004). Publisher Copyright: {\textcopyright} 2019 UICC",
year = "2019",
month = aug,
day = "15",
doi = "10.1002/ijc.32151",
language = "English (US)",
volume = "145",
pages = "1099--1110",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "4",
}
