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The purpose of this study was to investigate the effect of M2\u2010like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP\u20101) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP\u20101 and J774\u20101 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2\u2010like TAMs in transplanted lung cancer in mouse. We used the COX\u20102 inhibitor nimesulide to inhibit the secretion of MCP\u20101 and PGE2, which promotes macrophage migration and M2\u2010like differentiation. Nimesulide treatment decreased the secretion of MCP\u20101 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP\u20101. Lung cancer supernatant induced the differentiation of macrophages toward the M2\u2010like phenotype, and nimesulide treatment inhibited M2\u2010like differentiation by blocking MCP\u20101 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2\u2010like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP\u20101 and PGE2 from tumor cells depleted M2\u2010like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model.<\/jats:p>","DOI":"10.1111\/cas.15671","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T05:09:07Z","timestamp":1669093747000},"page":"750-763","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Depletion of tumor\u2010associated macrophages inhibits lung cancer growth and enhances the antitumor effect of cisplatin"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7828-4635","authenticated-orcid":false,"given":"Yo","family":"Kawaguchi","sequence":"first","affiliation":[{"name":"Division of General Thoracic Surgery, Department of Surgery Shiga University of Medical Science  Otsu 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