{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:14:50Z","timestamp":1788369290881,"version":"build-2803163510"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education Culture, Sports, Science, and Technology of Japan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Serous carcinoma of the uterus (USC) is a pathological subtype of high-grade endometrial cancers, with no effective treatment for advanced cases. Since such refractory tumors frequently harbor antitumor immune tolerance, many immunotherapies have been investigated for various malignant tumors using immuno-competent animal models mimicking their local immunities. In this study, we established an orthotopic mouse model of high-grade endometrial cancer and evaluated the local tumor immunity to explore the efficacy of immunotherapies against USC. A multivariate analysis of 62 human USC cases revealed that the tumor-infiltrating cell status, few CD8+ cells and abundant myeloid-derived suppressor cells (MDSCs), was an independent prognostic factor (P &amp;lt; 0.005). A murine endometrial cancer cell (mECC) was obtained from C57BL\/6 mice via endometrium-specific deletion of Pten and Tp53, and another high-grade cell (HPmECC) was established by further overexpressing Myc in mECCs. HPmECCs exhibited higher capacities of migration and anchorage-independent proliferation than mECCs (P &amp;lt; 0.01, P &amp;lt; 0.0001), and when both types of cells were inoculated into the uterus of C57BL\/6 mice, the prognosis of mice bearing HPmECC-derived tumors was significantly poorer (P &amp;lt; 0.001). Histopathological analysis of HPmECC orthotopic tumors showed serous carcinoma-like features with prominent tumor infiltration of MDSCs (P &amp;lt; 0.05), and anti-Gr-1 antibody treatment significantly prolonged the prognosis of HPmECC-derived tumor-bearing mice (P &amp;lt; 0.05). High CCL7 expression was observed in human USC and HPmECC, and MDSCs migration was promoted in a CCL7 concentration-dependent manner. These results indicate that antitumor immunity is suppressed in USC due to increased number of tumor-infiltrating MDSCs via CCL signal.<\/jats:p>","DOI":"10.1093\/carcin\/bgac032","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T03:14:00Z","timestamp":1648523640000},"page":"647-658","source":"Crossref","is-referenced-by-count":14,"title":["Immunosuppressive tumor microenvironment in uterine serous carcinoma via CCL7 signal with myeloid-derived suppressor cells"],"prefix":"10.1093","volume":"43","author":[{"given":"Yuka","family":"Mise","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine , Kyoto , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzo","family":"Hamanishi","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine , Kyoto , 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University Graduate School of Medicine , Kyoto , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1240-5422","authenticated-orcid":false,"given":"Koji","family":"Yamanoi","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine , Kyoto , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine , Kyoto , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayo","family":"Ukita","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine , Kyoto , 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Hosoe","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine , Kyoto , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumpei","family":"Terakawa","sequence":"additional","affiliation":[{"name":"Institute for Experimental Animals, Advanced Science Research Center, Kanazawa University , Kanazawa , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Kagabu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Shiwa , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-3557","authenticated-orcid":false,"given":"Tamotsu","family":"Sugai","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, Iwate Medical University School of Medicine , Shiwa , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsumasa","family":"Osakabe","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, Iwate Medical University School of Medicine , Shiwa , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science , Kanazawa , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriomi","family":"Matsumura","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kindai University School of Medicine , Sayama , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Mandai","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Kyoto University Graduate School 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Oncol."},{"key":"2022083013590199600_CIT0005","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated genomic characterization of endometrial carcinoma.","volume":"497","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"2022083013590199600_CIT0006","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1073\/pnas.1222577110","article-title":"Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma.","volume":"110","author":"Zhao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. 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