{"doi":"10.1136/jitc-2022-006303","title":"Specific recognition of an <i>FGFR2</i> fusion by tumor infiltrating lymphocytes from a patient with metastatic cholangiocarcinoma","abstract":"Background 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 fibroblast growth factor receptor 2 ( FGFR2 ) 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 FGFR2 fusions can be recognized by patients’ T cells. Method To address whether FGFR2 fusions can be recognized by patients’ T cells, we tested TILs from four patients with FGFR2 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. Results We found that CD4 + TILs from one patient specifically recognized the breakpoint region of a unique FGFR2-TDRD1 (tudor domain-containing 1) fusion, and we isolated a T-cell receptor responsible for its recognition. Conclusions This finding suggests that FGFR2 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 FGFR2 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.","journal":"Journal for ImmunoTherapy of Cancer","year":2023,"id":353751,"datarank":0.3331313962376412,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.021215164985665787,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.021215164985665787,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":6,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00068003"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":250441,"name":"Sivasish Sindiri","orcid":"0000-0003-2516-969X","position":1,"is_corresponding":false},{"id":226274,"name":"Victoria Hill","orcid":"0000-0003-2214-2459","position":2,"is_corresponding":false},{"id":225666,"name":"Billel Gasmi","orcid":"0000-0002-8061-8278","position":3,"is_corresponding":false},{"id":839458,"name":"Shirley Nah","orcid":"0000-0002-0916-1025","position":4,"is_corresponding":false},{"id":226275,"name":"Jared J. Gartner","orcid":"0000-0003-2924-3519","position":5,"is_corresponding":false},{"id":228785,"name":"Todd D. Prickett","orcid":"0000-0001-5466-4150","position":6,"is_corresponding":false},{"id":288537,"name":"Yong Li","orcid":"0000-0001-8838-1714","position":7,"is_corresponding":false},{"id":226272,"name":"Devikala Gurusamy","orcid":"0000-0002-1727-8653","position":8,"is_corresponding":false},{"id":226282,"name":"Paul F. Robbins","orcid":"0000-0002-1260-8123","position":9,"is_corresponding":false},{"id":226283,"name":"Steven A. Rosenberg","orcid":"0000-0002-8939-8910","position":10,"is_corresponding":false},{"id":228498,"name":"Vid Leko","orcid":"0000-0001-7883-5030","position":11,"is_corresponding":false},{"id":858441,"name":"Bradley S. White","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:13:02.680107Z","pmid":"37045473","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}