{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:14:15Z","timestamp":1790352855228,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Inhibition of the programmed cell death protein-1\/ligand-1 (PD-1\/PD-L1) axis has opened a new era in the treatment of solid cancers. However, there is no data on the expression and relevance of PD-L1 in Western gallbladder cancer (GBC). We assessed PD-L1 immunohistochemically in 131 GBC patients as Tumor Proportion Score (TPS), Immune Cell Score (IC) and Combined Positivity Score (CPS). Tumor cells expressed PD-L1 in a subset of 14.7% GBC patients at a TPS cut-off of 1%. Higher PD-L1 levels above 10% and 25% TPS were reached in 4.7% and 3.1% of GBC cases, respectively. At a 10% cut-off, TPS was associated with distinct histomorphological subtypes and correlated with poor tumor differentiation. Survival analysis revealed a TPS above 10% to be a highly significant and independent negative prognosticator in GBC. PD-L1 expression was associated with increased CD4+, CD8+ and PD-1+ immune cell densities. In 14.8% of the cases, scattered immune cells expressed T-cell immunoreceptor with Ig and ITIM domains (TIGIT), which was correlated to tumoral expression of its ligand CD155. We here show that a high PD-L1 expression confers a negative prognostic value in Western-world GBC and highlight the TIGIT\/CD155 immune checkpoint as a potential new target for GBC immunotherapy.<\/jats:p>","DOI":"10.3390\/cancers13071682","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T10:34:09Z","timestamp":1617359649000},"page":"1682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2234-0909","authenticated-orcid":false,"given":"Thomas","family":"Albrecht","sequence":"first","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz","family":"Brinkmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Albrecht","sequence":"additional","affiliation":[{"name":"European Center for Angioscience (ECAS), Medical Faculty of Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3582-7238","authenticated-orcid":false,"given":"Anke S.","family":"Lonsdorf","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianeb","family":"Mehrabi","sequence":"additional","affiliation":[{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"},{"name":"Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"},{"name":"Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakup","family":"Kulu","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alphonse","family":"Charbel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika N.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Radiology, Thoraxklinik at Heidelberg University Hospital, 69126 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2808-9230","authenticated-orcid":false,"given":"Christian","family":"Rupp","sequence":"additional","affiliation":[{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"},{"name":"Department of Internal Medicine IV, Gastroenterology and Hepatology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Springfeld","sequence":"additional","affiliation":[{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases, Department of Medical Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schirmacher","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5333-5942","authenticated-orcid":false,"given":"Stephanie","family":"Roessler","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Goeppert","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Liver Cancer Center Heidelberg (LCCH), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"ref_1","first-page":"99","article-title":"Gallbladder cancer: Epidemiology and outcome","volume":"6","author":"Hundal","year":"2014","journal-title":"Clin. 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