{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:13:52Z","timestamp":1789665232857,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T00:00:00Z","timestamp":1551225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004420","name":"Wakayama Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004420","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K16863"],"award-info":[{"award-number":["JP17K16863"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,4]]},"abstract":"Programmed cell death ligand 1 (PD<\/jats:styled-content>\u2010L1) on tumor cells suppresses anti\u2010tumor immunity and has an unfavorable prognostic impact in ovarian cancer patients. We herein report the pathophysiological and therapeutic impacts of PD<\/jats:styled-content>\u2010L1 disruption in ovarian cancer. PD<\/jats:styled-content>\u2010L1 was genetically disrupted in the murine ovarian cancer cell line ID<\/jats:styled-content>8 using clustered regularly interspaced short palindromic repeats (CRISPR<\/jats:styled-content>)\/Cas9\u2010mediated genome editing. PD<\/jats:styled-content>\u2010L1 knockout (KO<\/jats:styled-content>) and control ovarian cancer cells were intraperitoneally inoculated into syngeneic mice, and survival and tumor dissemination were evaluated. Survival times were significantly longer in the PD<\/jats:styled-content>\u2010L1\u2010KO ID<\/jats:styled-content>8\u2010inoculated groups than in their control groups, and its therapeutic benefit was enhanced in combination with the cisplatin treatment. Tumor weights and ascites volumes were significantly lower in the PD<\/jats:styled-content>\u2010L1\u2010KO ID<\/jats:styled-content>8 groups than in their control groups. Immunohistochemical and immunofluorescence analyses showed that intratumoral CD<\/jats:styled-content>4+<\/jats:sup> T cells, CD<\/jats:styled-content>8+<\/jats:sup> T cells, NK<\/jats:styled-content> cells and CD<\/jats:styled-content>11c+<\/jats:sup> M1 macrophages were significantly increased, whereas regulatory T cells were significantly decreased in the PD<\/jats:styled-content>\u2010L1\u2010KO ID<\/jats:styled-content>8 groups compared with those in their control groups. The intratumoral mRNA<\/jats:styled-content> expression of interferon\u2010\u03b3, tumor\u2010necrosis factor\u2010\u03b1, interleukin (IL<\/jats:styled-content>)\u20102, IL<\/jats:styled-content>\u201012a, CXCL<\/jats:styled-content>9 and CXCL<\/jats:styled-content>10 was significantly stronger, while that of IL<\/jats:styled-content>\u201010, vascular endothelial growth factor, CXCL<\/jats:styled-content>1 and CXCL<\/jats:styled-content>2 was significantly weaker in the PD<\/jats:styled-content>\u2010L1\u2010KO ID<\/jats:styled-content>8 groups. These results indicate that CRISPR<\/jats:styled-content>\/Cas9\u2010mediated PD<\/jats:styled-content>\u2010L1 disruption on tumor cells promotes anti\u2010tumor immunity by increasing tumor\u2010infiltrating lymphocytes and modulating cytokine\/chemokine profiles within the tumor microenvironment, thereby suppressing ovarian cancer progression. These results suggest that PD<\/jats:styled-content>\u2010L1\u2010targeted therapy by genome editing may be a novel therapeutic strategy for ovarian cancer.<\/jats:p>","DOI":"10.1111\/cas.13958","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T11:29:34Z","timestamp":1548934174000},"page":"1279-1292","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Programmed cell death ligand 1 d<\/scp>isruption by clustered regularly interspaced short palindromic repeats<\/scp>\/Cas9\u2010genome editing promotes antitumor immunity and suppresses ovarian cancer progression"],"prefix":"10.1111","volume":"110","author":[{"given":"Tamaki","family":"Yahata","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Orimo","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute of Advanced Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Toujima","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Kuninaka","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuho","family":"Nosaka","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute of Advanced Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Fukuda\u2010Ohta","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute of Advanced Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Hemmi","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute of Advanced Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Iwahashi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneyasu","family":"Kaisho","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute of Advanced Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6198-0730","authenticated-orcid":false,"given":"Kazuhiko","family":"Ino","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-016-0389-1"},{"key":"e_1_2_7_3_1","first-page":"17","volume-title":"Cancer Facts & Figures","author":"American Cancer Society","year":"2016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1586"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00442.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1936"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1102-991"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2010.01.019"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/70932"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.1027"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.05.016"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-016-0968-y"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxw020"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40661-016-0033-6"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611533104"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2199"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6429"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad7118"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.62.3397"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2015.33.15_suppl.5509"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6392"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1258096"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.07.030"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12445"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.09.039"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-3098"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/104063871102300102"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43027"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160801"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13072"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11406"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2017.209"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22396"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-2606"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.0513"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15520"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1938"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.25961"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24191"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.4172\/2155-9899.1000371"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-10-0107"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7700876"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.01.001"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad5177"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04625-5"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.13958","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13958","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.13958","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111%2Fcas.13958","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13958","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T20:30:08Z","timestamp":1694377808000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.13958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,27]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/cas.13958"],"URL":"https:\/\/doi.org\/10.1111\/cas.13958","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,27]]},"assertion":[{"value":"2018-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}