{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:01:03Z","timestamp":1787241663517,"version":"build-2736575974"},"reference-count":34,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"unspecified","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Cooperative Research and Development Agreement between NCI and Iovance Biotechnology","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"National Cancer Institute Center for Cancer Research","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Cooperative Research and Development Agreement between NCI and Neogene Therapeutics","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,4,13]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neoantigen-specific tumor-infiltrating lymphocytes (TILs) have the ability to mediate responses in patients with metastatic epithelial cancers. While some identified factors are associated with response, there is a need for ways to determine which patients will benefit from adoptive cell therapy with TIL. Patient-derived tumor organoids (PDTO) retain the genetic makeup of the tumor from which they are derived, and are a useful tool in personalized medicine to test the effectiveness of anticancer therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tumor organoids were grown from patients with metastatic epithelial cancers treated on a TIL protocol. TIL recognition of autologous PDTO by enzyme-linked immunosorbent spot assays and 4\u20131BB upregulation, as well as objective Response Evaluation Criteria in Solid Tumors (RECIST) responses to treatment, were measured in a cohort of treated patients. The most common histologies were colorectal (20 patients, 67%), pancreatic (4 patients, 13%), and breast (2 patients, 7%) cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Recognition of PDTO was driven by major histocompatibility complex (MHC) class I-restricted reactivity and upregulation of MHC in response to interferon-\u03b3 was not associated with response. There were no responders in the 9 patients who lacked PDTO recognition on their initial TIL screening compared with seven responses in 18 patients with initial reactivity (p=0.059). After TIL were selected and expanded for administration, 15 infusion products showed organoid recognition, with 8 of these patients achieving objective responses (53%), while only 1 of 15 patients without organoid recognition responded (7%; p=0.014).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TIL reactivity against autologous tumor organoid appears to be associated with objective clinical response in patients with metastatic epithelial cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014644","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:40:12Z","timestamp":1778082012000},"page":"e014644","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Correlation between recognition of autologous tumor organoids by tumor-infiltrating lymphocytes from metastatic epithelial cancers and clinical response"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct00068003","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"}],"author":[{"given":"Alexandra M","family":"Gustafson","sequence":"first","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"},{"name":"Surgery, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarushi","family":"Bhasin","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billel","family":"Gasmi","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"},{"name":"Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8998-3292","authenticated-orcid":false,"given":"Brian D","family":"Bui","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-6258","authenticated-orcid":false,"given":"Catherine Marie","family":"Ade","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Hanada","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunmi K","family":"Halas","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared J","family":"Gartner","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd D","family":"Prickett","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Salazar","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R","family":"Parkhust","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, 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 Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D","family":"Klemen","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Li","family":"Kwong","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3317-9804","authenticated-orcid":false,"given":"Stephanie L","family":"Goff","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-5008","authenticated-orcid":false,"given":"James C","family":"Yang","sequence":"additional","affiliation":[{"name":"Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"2026050608400811000_14.5.e014644.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251102"},{"key":"2026050608400811000_14.5.e014644.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0040-8"},{"key":"2026050608400811000_14.5.e014644.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.9093"},{"key":"2026050608400811000_14.5.e014644.4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.5449"},{"key":"2026050608400811000_14.5.e014644.5","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1038\/s41591-025-03627-5","article-title":"Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial","volume":"31","author":"Lowery","year":"2025","journal-title":"Nat Med"},{"key":"2026050608400811000_14.5.e014644.6","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3161"},{"key":"2026050608400811000_14.5.e014644.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406498"},{"key":"2026050608400811000_14.5.e014644.8","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3682"},{"key":"2026050608400811000_14.5.e014644.9","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1494"},{"key":"2026050608400811000_14.5.e014644.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.082."},{"key":"2026050608400811000_14.5.e014644.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2013.11.012"},{"key":"2026050608400811000_14.5.e014644.12","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1007\/s00262-023-03476-6","article-title":"Using patient-derived tumor organoids from common epithelial cancers to analyze personalized T-cell responses to neoantigens","volume":"72","author":"Parikh","year":"2023","journal-title":"Cancer Immunol Immunother"},{"key":"2026050608400811000_14.5.e014644.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.009"},{"key":"2026050608400811000_14.5.e014644.14","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003213","article-title":"Empirical identification and validation of tumor-targeting T cell receptors from circulation using autologous pancreatic tumor organoids","volume":"9","author":"Meng","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026050608400811000_14.5.e014644.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.036"},{"key":"2026050608400811000_14.5.e014644.16","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2018100928","article-title":"3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids","volume":"38","author":"Schnalzger","year":"2019","journal-title":"EMBO J"},{"key":"2026050608400811000_14.5.e014644.17","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0833"},{"key":"2026050608400811000_14.5.e014644.18","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-0982"},{"key":"2026050608400811000_14.5.e014644.19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1604958"},{"key":"2026050608400811000_14.5.e014644.20","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0672"},{"key":"2026050608400811000_14.5.e014644.21","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/s41586-023-06199-x","article-title":"CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours","volume":"618","author":"Kruse","year":"2023","journal-title":"Nature New Biol"},{"key":"2026050608400811000_14.5.e014644.22","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200307000-00005"},{"key":"2026050608400811000_14.5.e014644.23","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2023.101335","article-title":"Unified framework for patient-derived, tumor-organoid-based predictive testing of standard-of-care therapies in metastatic colorectal cancer","volume":"4","author":"Tan","year":"2023","journal-title":"Cell Rep Med"},{"key":"2026050608400811000_14.5.e014644.24","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aay2574","article-title":"Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients","volume":"11","author":"Ooft","year":"2019","journal-title":"Sci Transl Med"},{"key":"2026050608400811000_14.5.e014644.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107762"},{"key":"2026050608400811000_14.5.e014644.26","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/s41416-019-0616-1","article-title":"Patient-derived organoids as a potential model to predict response to PD-1\/PD-L1 checkpoint inhibitors","volume":"121","author":"Scognamiglio","year":"2019","journal-title":"Br J Cancer"},{"key":"2026050608400811000_14.5.e014644.27","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-019-08143-8"},{"key":"2026050608400811000_14.5.e014644.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2024.11.010"},{"key":"2026050608400811000_14.5.e014644.29","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb9847"},{"key":"2026050608400811000_14.5.e014644.30","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-006264","article-title":"Cell surface marker-based capture of neoantigen-reactive CD8+ T-cell receptors from metastatic tumor digests","volume":"11","author":"Chatani","year":"2023","journal-title":"J Immunother Cancer"},{"key":"2026050608400811000_14.5.e014644.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0312-6"},{"key":"2026050608400811000_14.5.e014644.32","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-008645","article-title":"Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes","volume":"12","author":"Levin","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2026050608400811000_14.5.e014644.33","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.74.5463"},{"key":"2026050608400811000_14.5.e014644.34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0800251"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-014644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T15:40:14Z","timestamp":1778082014000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-014644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,6]]},"published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1136\/jitc-2025-014644"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-014644","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]}}}