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Due to the difficulty of achieving curative surgical resection in most patients with MPM, a combination chemotherapy of cisplatin and pemetrexed has been the only approved regimen proven to improve the prognosis of MPM. However, the median overall survival time is at most 12\u00a0mo even with this regimen. There has been therefore a pressing need to develop a novel chemotherapeutic strategy to bring about a better outcome for MPM. We found that expression of interleukin\u20101 receptor (IL\u20101R) was upregulated in MPM cells compared with normal mesothelial cells. We also investigated the biological significance of the interaction between pro\u2010inflammatory cytokine IL\u20101\u03b2 and the IL\u20101R in MPM cells. Stimulation by IL\u20101\u03b2 promoted MPM cells to form spheroids along with upregulating a cancer stem cell marker CD26. We also identified tumor\u2010associated macrophages (TAMs) as the major source of IL\u20101\u03b2 in the MPM microenvironment. Both high mobility group box 1 derived from MPM cells and the asbestos\u2010activated inflammasome in TAMs induced the production of IL\u20101\u03b2, which resulted in enhancement of the malignant potential of MPM. We further performed immunohistochemical analysis using clinical MPM samples obtained from patients who were treated with the combination of platinum plus pemetrexed, and found that the overexpression of IL\u20101R tended to correlate with poor overall survival. In conclusion, the interaction between MPM cells and TAMs through a IL\u20101\u03b2\/IL\u20101R signal could be a promising candidate as the target for novel treatment of MPM (Hyogo College of Medicine clinical trial registration number: 2973).<\/jats:p>","DOI":"10.1111\/cas.14523","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T13:10:45Z","timestamp":1591967445000},"page":"2895-2906","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Tumor\u2010associated macrophage\u2010derived inflammatory cytokine enhances malignant potential of malignant pleural mesothelioma"],"prefix":"10.1111","volume":"111","author":[{"given":"Daisuke","family":"Horio","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Hematology Hyogo College of Medicine  Nishinomiya 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