{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:17:07Z","timestamp":1783487827560,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatobiliary carcinoma (HBC) ranks as the sixth most prevalent cancer worldwide. Orthotopic liver transplantation (OLT) has emerged as a highly effective treatment option for early-stage HBC. Immunotherapies as neoadjuvant options are now being actively investigated in the transplant oncology era. This study reports our institutional experience in patients with HBC who had received immune checkpoint inhibitors (ICPI) prior to curative OLT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort included 25 patients with HBC [17 with HCC and eight with cholangiocarcinoma (CCA)], who received ICPI prior to OLT at a single institution from January 2019 to December 2025. Graft rejection was assessed and reported along with the type of ICPI, tumor features, locoregional therapies (LRTs), and the timing of ICPI in association with OLT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All 25 patients with HBC underwent OLT after neoadjuvant ICPI. A total of 19 patients were men, and six were women with a median age of 55 (interquartile range: 36\u201374) years at OLT. All patients received ICPI, including combinations of PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors. Liver-directed\/locoregional therapies were utilized in most cases, including transarterial chemoembolization (TACE), yttrium-90 (Y90), stereotactic body radiotherapy (SBRT), and radiofrequency ablation (RFA). The median washout period was 4.5 months. All patients responded to ICPI and achieved a safe and successful OLT. Most patients received tacrolimus plus mycophenolate as immunosuppressant (IS) therapy post-OLT, with 17 patients requiring additional IS, including prednisone or everolimus. One patient experienced immediate graft failure on the day of transplant, was made anhepatic, and was successfully retransplanted on the following day. Three patients experienced acute rejection during the first year post-transplant (two with liver rejection and one with kidney rejection following a deceased donor kidney transplant that was performed in conjunction with OLT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study highlights the potential of ICPI to achieve tumor downstaging prior to OLT in patients with HBC when given as a neoadjuvant therapy. In addition, this study illustrated the importance of timing for the administration of ICPI before OLT. Given the lack of conclusive evidence in this therapeutic area, these findings lay the groundwork for prospective trials to further examine the impact of ICPI in the pre-transplant setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1866870","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:53:24Z","timestamp":1783486404000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Utilization of immunotherapy as a neoadjuvant treatment in liver transplant recipients with hepatobiliary carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Maen","family":"Abdelrahim","sequence":"first","affiliation":[{"name":"Section of Gastrointestinal Oncology, Houston Methodist Neal Cancer Center","place":["Houston, TX, United States"]},{"name":"Department of Medicine, Weill Cornell Medical College","place":["New York, NY, United States"]},{"name":"Department of Medicine, Faculty of Medicine, The University of Jordan","place":["Amman, Jordan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Esmail","sequence":"additional","affiliation":[{"name":"Section of Gastrointestinal Oncology, Houston Methodist Neal Cancer Center","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashton A.","family":"Connor","sequence":"additional","affiliation":[{"name":"JC Walter Jr Center for Transplantation, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Kodali","sequence":"additional","affiliation":[{"name":"JC Walter Jr Center for Transplantation, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Saharia","sequence":"additional","affiliation":[{"name":"JC Walter Jr Center for Transplantation, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"David W.","family":"Victor","sequence":"additional","affiliation":[{"name":"JC Walter Jr Center for Transplantation, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline J.","family":"Simon","sequence":"additional","affiliation":[{"name":"JC Walter Jr Center for Transplantation, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Lee","family":"Cheah","sequence":"additional","affiliation":[{"name":"JC Walter Jr Center for Transplantation, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunyoung S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milind","family":"Javle","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed O.","family":"Kaseb","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafik Mark","family":"Ghobrial","sequence":"additional","affiliation":[{"name":"JC Walter Jr Center for Transplantation, Houston Methodist Hospital","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1053\/j.gastro.2020.02.068","article-title":"Global burden of 5 major types of gastrointestinal cancer","volume":"159","author":"Arnold","year":"2020","journal-title":"Gastroenterology"},{"key":"B3","article-title":"Global cancer observatory","volume":"23","author":"Ferlay","year":"2018","journal-title":"Cancer Today"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-021269","article-title":"Comparative efficacy of treatment strategies for hepatocellular carcinoma: systematic review and network meta-analysis","volume":"8","author":"Tian","year":"2018","journal-title":"BMJ Open"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00270-012-0394-0","article-title":"Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: Five-year survival analysis","volume":"35","author":"Malagari","year":"2012","journal-title":"Cardiovasc Interventional Radiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/hep.31288","article-title":"Epidemiology of hepatocellular carcinoma","author":"McGlynn","year":"2021","journal-title":"Hepatology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2008.01.005","article-title":"Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention","volume":"659","author":"Anwar","year":"2008","journal-title":"Mutat Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.canlet.2008.10.040","article-title":"Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection","volume":"286","author":"Chuang","year":"2009","journal-title":"Cancer Lett"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199603143341104","article-title":"Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis","volume":"334","author":"Mazzaferro","year":"1996","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13194911","article-title":"Transplant oncology: An evolving field in cancer care","volume":"13","author":"Abdelrahim","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15225337","article-title":"Transplant oncology: An emerging discipline of cancer treatment","volume":"15","author":"Abdelrahim","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-443-21901-6.00024-0","article-title":"Patient characteristics and evaluations prior to liver transplantation","volume-title":"Transplant Oncology","author":"Abdelrahim","year":"2025"},{"key":"B13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/B978-0-443-21901-6.00008-2","article-title":"Transplant oncology and immunotherapy: Immunotherapy and liver transplants","volume-title":"Transplant Oncology","author":"Abdelrahim","year":"2025"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100781","article-title":"Optimal treatment for small HCC (<3 cm): Resection, liver transplantation, or locoregional therapy","volume":"5","author":"Wu","year":"2023","journal-title":"Jhep Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1200\/op.21.00227","article-title":"Redefining intermediate-stage HCC treatment in the era of immune therapies","volume":"18","author":"Brar","year":"2022","journal-title":"Jco Oncol Pract"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16132369","article-title":"Advances in immunotherapy for transplant oncology","volume":"16","author":"Abdelrahim","year":"2024","journal-title":"Cancers"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.35516\/jmj.v59i1.3957","article-title":"Evaluating standardization of neoadjuvant immunotherapy in transplant-eligible hepatocellular carcinoma populations","volume":"59","author":"Esmail","year":"2025","journal-title":"Jordan Med J"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4103\/apjon.apjon_4_17","article-title":"Immune checkpoint inhibitors: An innovation in immunotherapy for the treatment and management of patients with cancer","volume":"4","author":"Dine","year":"2017","journal-title":"Asia Pac J Oncol Nurs"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1915745","article-title":"Atezolizumab plus\u00a0bevacizumab in unresectable hepatocellular carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N Engl J Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1056\/evidoa2100070","article-title":"Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma","volume":"1","author":"Abou-Alfa","year":"2022","journal-title":"NEJM Evidence"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/sla.0000000000000710","article-title":"Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis","volume":"261","author":"Tabrizian","year":"2015","journal-title":"Ann Surg"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(23)01796-8","article-title":"Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial","volume":"402","author":"Qin","year":"2023","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0829-0","article-title":"Learning from clinical trials of neoadjuvant checkpoint blockade","volume":"26","author":"Versluis","year":"2020","journal-title":"Nat Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N Engl J Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2217\/hep-2016-0007","article-title":"Regorafenib and the RESORCE trial: a new second-line option for hepatocellular carcinoma patients","volume":"3","author":"Bruix","year":"2016","journal-title":"Hepat Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.05.028","article-title":"Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study","volume":"49","author":"Bruix","year":"2013","journal-title":"Eur J Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-020-01378-y","article-title":"Cabozantinib in hepatocellular carcinoma","volume":"379","author":"Abou-Alfa","year":"2018","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx015","article-title":"Cabozantinib: targeted therapy back to the future","volume":"28","author":"Abou-Alfa","year":"2017","journal-title":"Ann Oncol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1056\/nejmoa1717002","article-title":"Cabozantinib in patients with advanced and progressing hepatocellular carcinoma","volume":"379","author":"Abou-Alfa","year":"2018","journal-title":"N Engl J Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(18)30351-6","article-title":"Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial","volume":"19","author":"Zhu","year":"2018","journal-title":"Lancet Oncol"},{"key":"B32","doi-asserted-by":"crossref","DOI":"10.1055\/s-0030-1247132","article-title":"Modified RECIST (mRECIST) assessment for hepatocellular carcinoma","volume-title":"Seminars in Liver Disease","author":"Lencioni","year":"2010"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1056\/evidoa2200015","article-title":"Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer","volume":"1","author":"Oh","year":"2022","journal-title":"NEJM Evidence"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol29060341","article-title":"Immunotherapy as a neoadjuvant therapy for a patient with hepatocellular carcinoma in the pretransplant setting: A case report","volume":"29","author":"Abdelrahim","year":"2022","journal-title":"Curr Oncol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.s322289","article-title":"Current landscape and future directions of biomarkers for immunotherapy in hepatocellular carcinoma","volume":"8","author":"Gok Yavuz","year":"2021","journal-title":"J Hepatocell Carcinoma"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.09.035","article-title":"Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score","volume":"76","author":"Scheiner","year":"2022","journal-title":"J Hepatol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1159\/000519448","article-title":"Early changes in alpha-fetoprotein are a useful predictor of efficacy of atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma","volume":"100","author":"Kuzuya","year":"2022","journal-title":"Oncology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.iliver.2024.100083","article-title":"Emerging role of molecular diagnosis and personalized therapy for hepatocellular carcinoma","volume":"3","author":"Wang","year":"2024","journal-title":"Iliver"},{"key":"B39","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s13046-021-01940-8","article-title":"Current status of ctDNA in precision oncology for hepatocellular carcinoma","volume":"40","author":"Li","year":"2021","journal-title":"J Exp Clin Cancer Res"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1866870\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:53:34Z","timestamp":1783486414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1866870\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":39,"alternative-id":["10.3389\/fonc.2026.1866870"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1866870","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,8]]},"article-number":"1866870"}}