{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:49:01Z","timestamp":1789750141703,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA231325"],"award-info":[{"award-number":["CA231325"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tumor cell\u2010intrinsic programmed death\u2010ligand 1 (PD\u2010L1) signals mediate immunopathologic effects in breast, colon, and ovarian cancers and in melanomas, but bladder cancer (BC) effects are unreported. We show here that BC cell\u2010intrinsic PD\u2010L1 signals in mouse MB49 and human RT4, UM\u2010UC3, and UM\u2010UC\u201014 BC cells regulate important pathologic pathways and processes, including effects not reported in other cancers. \u03b1\u2010PD\u2010L1 antibodies reduced BC cell proliferation in vitro, demonstrating direct signaling effects. BC cell\u2010intrinsic PD\u2010L1 promoted mammalian target of rapamycin complex 1 (mTORC1) signals in vitro and augmented in vivo immune\u2010independent cell growth and metastatic cancer spread, similar to effects we reported in melanoma and ovarian cancer. BC cell\u2010intrinsic PD\u2010L1 signals also promoted basal and stress\u2010induced autophagy, whereas these signals inhibited autophagy in melanoma and ovarian cancer cells. BC cell\u2010intrinsic PD\u2010L1 also mediated chemotherapy resistance to the commonly used BC chemotherapy agents cis\u2010platinum and gemcitabine and to the mTORC1 inhibitor, rapamycin. Thus, BC cell\u2010intrinsic PD\u2010L1 signals regulate important virulence and treatment resistance pathways that suggest novel, actionable treatment targets meriting additional studies. As a proof\u2010of\u2010concept, we showed that the autophagy inhibitor chloroquine improved cis\u2010platinum treatment efficacy in vivo, with greater efficacy in PD\u2010L1 null versus PD\u2010L1\u2010replete BC.<\/jats:p>","DOI":"10.1002\/cam4.3739","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T17:50:52Z","timestamp":1614189052000},"page":"2137-2152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Bladder cancer cell\u2010intrinsic PD\u2010L1 signals promote mTOR and autophagy activation that can be inhibited to improve cytotoxic chemotherapy"],"prefix":"10.1002","volume":"10","author":[{"given":"Deyi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9562-5809","authenticated-orcid":false,"given":"Ryan M.","family":"Reyes","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences University of Texas Health San Antonio TX USA"},{"name":"Department of Microbiology, Immunology and Molecular Genetics University Texas Health San Antonio TX USA"},{"name":"Mays Cancer Center, University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Osta","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences University of Texas Health San Antonio TX USA"},{"name":"Department of Microbiology, Immunology and Molecular Genetics University Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Kari","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshita B.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro S.","family":"Padron","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand V. R.","family":"Kornepati","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Sciences University of Texas Health San Antonio TX USA"},{"name":"Department of Microbiology, Immunology and Molecular Genetics University Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-7735","authenticated-orcid":false,"given":"Aravind","family":"Kancharla","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujie","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilun","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1654-198X","authenticated-orcid":false,"given":"Bogang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2849-4076","authenticated-orcid":false,"given":"Ratna","family":"Vadlamudi","sequence":"additional","affiliation":[{"name":"Mays Cancer Center, University of Texas Health San Antonio TX USA"},{"name":"Department of Obstetrics and Gynecology University of Texas Health Science Center San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[{"name":"Mays Cancer Center, University of Texas Health San Antonio TX USA"},{"name":"Department of Molecular Medicine University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0239-1338","authenticated-orcid":false,"given":"Robert S.","family":"Svatek","sequence":"additional","affiliation":[{"name":"Mays Cancer Center, University of Texas Health San Antonio TX USA"},{"name":"Department of Urology University of Texas Health Science Center San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6962-9411","authenticated-orcid":false,"given":"Tyler J.","family":"Curiel","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Texas Health San Antonio TX USA"},{"name":"Graduate School of Biomedical Sciences University of Texas Health San Antonio TX USA"},{"name":"Department of Microbiology, Immunology and Molecular Genetics University Texas Health San Antonio TX USA"},{"name":"Mays Cancer Center, University of Texas Health San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003496"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S105862"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894-018-0414-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2017.04.014"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30616-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.2411"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00561-4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30065-7"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.7_suppl.350"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad7118"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0191-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00386"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0258"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2016.30"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1114"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000496"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm863"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0176"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003586"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.01.009"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep38531"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-180167"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10010018"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1474314"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.080796"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16326"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2018.e01039"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0697-x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-019-0919-y"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-1108"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajur.2018.06.006"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10824"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-5-200603070-00008"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000486222"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kjms.2017.01.004"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1586\/era.11.201"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.3739","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.3739","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.3739","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T10:20:26Z","timestamp":1693563626000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.3739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1002\/cam4.3739"],"URL":"https:\/\/doi.org\/10.1002\/cam4.3739","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]},"assertion":[{"value":"2020-10-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}