{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T23:21:23Z","timestamp":1788823283910,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gallbladder cancer (GBC) is one of the most common and aggressive biliary tract cancers with a dismal prognosis. Ongoing clinical trials are evaluating a few selected immune checkpoint inhibitors (ICIs) as monotherapy for the treatment of GBC patients. However, only a subset of patients benefits from these treatments. To improve ICI therapy response, molecular mechanisms that confer resistance to immune checkpoint (IC) blockade needs to be explored. Epithelial-to-mesenchymal transition (EMT) program and cancer stem cells (CSCs) have been implicated as key processes that confer ICI treatment resistance. However, in GBC the EMT-CSC-IC axis has not yet been clearly elucidated. This study aims to examine the aberrant expression of ICs associated with CSC and EMT. We successfully enriched CSCs by utilizing a 3-dimensional culture system and established a reversible EMT model with human GBC NOZ cell line. Notably, ICs CD73 and PD-L1 were closely associated with both CSC and EMT phenotypes. Knockdown of CD73 or PD-L1 reduced the proliferative and motile abilities of both adherent monolayers and anchorage-free spheroids. In conclusion, blocking CD73 and PD-L1 offer a promising therapeutic strategy for targeting highly aggressive populations with CSC and EMT phenotype to improve GBC patient prognosis.<\/jats:p>","DOI":"10.3390\/ijms23031565","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T23:02:06Z","timestamp":1643497326000},"page":"1565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer"],"prefix":"10.3390","volume":"23","author":[{"given":"Lu","family":"Cao","sequence":"first","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, QLD 4120, Australia"},{"name":"Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim R.","family":"Bridle","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, QLD 4120, Australia"},{"name":"Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-6169","authenticated-orcid":false,"given":"Ritu","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, QLD 4120, Australia"},{"name":"Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth","family":"Prithviraj","sequence":"additional","affiliation":[{"name":"Fiona Elsey Cancer Research Institute, Ballarat, VIC 3350, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell H. G.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, QLD 4120, Australia"},{"name":"Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna","family":"Jayachandran","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, QLD 4120, Australia"},{"name":"Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia"},{"name":"Fiona Elsey Cancer Research Institute, Ballarat, VIC 3350, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"ref_1","unstructured":"(2021, September 01). 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