{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:30:30Z","timestamp":1784719830932,"version":"3.55.0"},"reference-count":52,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"unspecified","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,3,23]]},"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Metastatic cholangiocarcinoma (CC), a form of gastrointestinal cancer that originates from the bile ducts, cannot be cured by currently available therapies, and is associated with dismal prognosis. In a previous case report, adoptive transfer of autologous tumor infiltrating lymphocytes (TILs), the majority of which recognized a tumor-specific point mutation, led to a profound and durable cancer regression in a patient with metastatic CC. Thus, more effective treatment for patients with this disease may be developed by using TILs that target cancer-specific mutations, but also other genetic aberrations such as gene fusions. In this context, fusions that involve <jats:italic>fibroblast growth factor receptor 2<\/jats:italic> (<jats:italic>FGFR2<\/jats:italic>) and function as oncogenes in a subset of patients with intrahepatic CC (ICC) represent particularly attractive targets for adoptive cell therapy. However, no study to date has explored whether <jats:italic>FGFR2<\/jats:italic> fusions can be recognized by patients\u2019 T cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Method<\/jats:title>\n                  <jats:p>To address whether <jats:italic>FGFR2<\/jats:italic> fusions can be recognized by patients\u2019 T cells, we tested TILs from four patients with <jats:italic>FGFR2<\/jats:italic> fusion-positive ICC for recognition of peptides and minigenes that represented the breakpoint regions of these fusions, which were unique to each of the four patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found that CD4<jats:sup>+<\/jats:sup> TILs from one patient specifically recognized the breakpoint region of a unique <jats:italic>FGFR2-TDRD1 (tudor domain-containing 1)<\/jats:italic> fusion, and we isolated a T-cell receptor responsible for its recognition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This finding suggests that <jats:italic>FGFR2<\/jats:italic> fusion-reactive TILs can be isolated from some patients with metastatic ICC, and thus provides a rationale for future exploration of T cell-based therapy targeting <jats:italic>FGFR2<\/jats:italic> fusions in patients with cancer. Furthermore, it augments the rationale for extending such efforts to other types of solid tumors hallmarked by oncogenic gene fusions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2022-006303","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T13:00:23Z","timestamp":1681304423000},"page":"e006303","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Specific recognition of an <i>FGFR2<\/i> fusion by tumor infiltrating lymphocytes from a patient with metastatic cholangiocarcinoma"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct01174121","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01174121","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01174121","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04102436","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00068003","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Bradley Sinclair","family":"White","sequence":"first","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2516-969X","authenticated-orcid":false,"given":"Sivasish","family":"Sindiri","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Hill","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billel","family":"Gasmi","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Nah","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared J","family":"Gartner","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd D","family":"Prickett","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Li","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devikala","family":"Gurusamy","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1260-8123","authenticated-orcid":false,"given":"Paul","family":"Robbins","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7883-5030","authenticated-orcid":false,"given":"Vid","family":"Leko","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA"},{"name":"Immune Deficiency Cellular Therapy Program, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"2025100307461333000_11.4.e006303.1","article-title":"Incidence of cholangiocarcinoma in the USA from 2001 to 2015: A US cancer statistics analysis of 50 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