{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:10:05Z","timestamp":1790237405472,"version":"4.1.0"},"reference-count":13,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"unspecified","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cluster of Excellence 2180 \"Image-guided and Functionally Instructed Tumor Therapies\u201d","award":["EXC 2180 - 390900677"],"award-info":[{"award-number":["EXC 2180 - 390900677"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,9,3]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>\n                    Cholangiocarcinomas are rare but aggressive liver tumors of high lethality with scarce treatment options. Here we report on the follow-up of a patient diagnosed with an intrahepatic cholangiocarcinoma who experienced repeated tumor recurrences including distant metastasis, therefore facing a dismal prognosis. At present, this patient is tumor-free for more than 8 years following repeated surgery and application of two successive personalized vaccines. In-depth functional immune cell analyses revealed a dominant CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell response against the vaccine antigens with infiltration of the tumor site and immune responses prevailing for years following the last vaccine administration. Additionally, spontaneous tumor neoantigen-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses have been detected, which might have contributed to the outstanding outcome witnessed in this patient. This case report highlights vaccination strategies targeting non-mutated antigens as well as the increasingly recognized central role of antitumor CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells.\n                  <\/jats:p>","DOI":"10.1136\/jitc-2025-012107","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:10:17Z","timestamp":1760011817000},"page":"e012107","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Exceptional tumor-free survival of a patient with metastatic intrahepatic cholangiocarcinoma after surgery and personalized peptide vaccination: revisiting a striking case"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1261-7211","authenticated-orcid":false,"given":"Ana","family":"Maia","sequence":"first","affiliation":[{"name":"Institute of Immunology, University and University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Schuhmacher","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University and University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio","family":"Nadalin","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"K\u00f6nigsrainer","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7328-7589","authenticated-orcid":false,"given":"Karolin","family":"Thiel","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Department of General, Visceral and Thoracic Surgery, Oberschwabenklinik gGmbH, St. Elisabethen-Klinikum, Ravensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-8481","authenticated-orcid":false,"given":"Annika","family":"Nelde","sequence":"additional","affiliation":[{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Institute of Immunology, Department of Peptide-based Immunotherapy, University and University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael S","family":"Zinser","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University and University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-3012","authenticated-orcid":false,"given":"Christopher","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site T\u00fcbingen, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7362-0209","authenticated-orcid":false,"given":"Sven","family":"Mattern","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Singer","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-435X","authenticated-orcid":false,"given":"Hans","family":"B\u00f6sm\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1614-2647","authenticated-orcid":false,"given":"Hans-Georg","family":"Rammensee","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University and University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site T\u00fcbingen, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-1317","authenticated-orcid":false,"given":"Markus W","family":"L\u00f6ffler","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University and University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site T\u00fcbingen, Heidelberg, Germany"},{"name":"Institute for Clinical and Experimental Transfusion Medicine (IKET), University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6410-2378","authenticated-orcid":false,"given":"C\u00e9cile","family":"Gouttefangeas","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University and University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u2018Image-Guided and Functionally Instructed Tumor Therapies\u2019, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site T\u00fcbingen, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"2026052722304716000_13.10.e012107.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00741-4"},{"key":"2026052722304716000_13.10.e012107.2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1001\/jamasurg.2013.5137","article-title":"Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma: Systematic Review and Meta-analysis","volume":"149","author":"Mavros","year":"2014","journal-title":"JAMA Surg"},{"key":"2026052722304716000_13.10.e012107.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251102"},{"key":"2026052722304716000_13.10.e012107.4","doi-asserted-by":"crossref","DOI":"10.3390\/vaccines11061062","article-title":"Cholangiocarcinoma in the Era of Immunotherapy","volume":"11","author":"Manthopoulou","year":"2023","journal-title":"Vaccines (Basel)"},{"key":"2026052722304716000_13.10.e012107.5","doi-asserted-by":"publisher","DOI":"10.21037\/hbsn-20-396"},{"key":"2026052722304716000_13.10.e012107.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.06.027"},{"key":"2026052722304716000_13.10.e012107.7","doi-asserted-by":"crossref","DOI":"10.1186\/s40425-019-0796-5","article-title":"A new synthetic toll-like receptor 1\/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer","volume":"7","author":"Rammensee","year":"2019","journal-title":"J Immunother Cancer"},{"key":"2026052722304716000_13.10.e012107.8","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELL.2020.05.017"},{"key":"2026052722304716000_13.10.e012107.9","doi-asserted-by":"crossref","first-page":"596","DOI":"10.3390\/cancers13040596","article-title":"CD4+ T Cells: Multitasking Cells in the Duty of Cancer Immunotherapy","volume":"13","author":"Richardson","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2026052722304716000_13.10.e012107.10","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abe3348","article-title":"Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer","volume":"7","author":"Cachot","year":"2021","journal-title":"Sci Adv"},{"key":"2026052722304716000_13.10.e012107.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0810-y"},{"key":"2026052722304716000_13.10.e012107.12","doi-asserted-by":"publisher","DOI":"10.1038\/nature23003"},{"key":"2026052722304716000_13.10.e012107.13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.8053"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-012107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:31:18Z","timestamp":1779946278000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-012107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":13,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,9]]},"published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1136\/jitc-2025-012107"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-012107","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]}}}