{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:32:59Z","timestamp":1792092779076,"version":"4.4.0"},"reference-count":110,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"unspecified","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,3,20]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>Autologous tumor-infiltrating lymphocyte (TIL) therapy has recently been approved by the US Food and Drug Administration and Health Canada for the management of patients with advanced melanoma refractory to first-line immune checkpoint inhibitors, with regulatory assessments underway in other jurisdictions. TIL therapy typically involves a multistep process including surgical tumor resection, non-myeloablative lymphodepletion, infusion of autologous polyclonal T cells, and administration of high-dose interleukin-2 (HD-IL-2). Toxicities are predominantly associated with the induction chemotherapy regimen and post-TIL infusion HD-IL-2, rather than the TIL product itself. Over half of treated patients experience cytopenias, pyrexia, rigors, and gastrointestinal symptoms, with additional toxicities including acute kidney injury, rash, peripheral neuropathy, diarrhea, alopecia, and hypotension. Severe but less frequent adverse events include neutropenic sepsis, cytokine release syndrome, capillary leak syndrome, neurotoxicity, autoimmune sequelae, and cardiac dysfunction. These toxicities typically occur in a predictable temporal window and resolve within 10\u201312\u2009days post-TIL infusion. Despite this, management often requires rigorous supportive care, and thus, toxicity remains a barrier to broader patient eligibility and wider implementation. Currently, no validated biomarkers exist to predict toxicity risk, underscoring the need for further research. This is particularly critical in the context of emerging combinatorial approaches integrating TIL therapy with other immunomodulatory agents, which may compound toxicity and complicate clinical management.<\/jats:p>","DOI":"10.1136\/jitc-2025-014378","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T16:15:32Z","timestamp":1775751332000},"page":"e014378","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["HosTIL territory: mapping the landscape of toxicity in TIL therapy"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct06940739","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06828328","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9470-314X","authenticated-orcid":false,"given":"Rachel","family":"Woodford","sequence":"first","affiliation":[{"name":"Advanced Immunotherapy and Cell Therapy, The Christie NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jose","family":"Demiguelarroyo","sequence":"additional","affiliation":[{"name":"Hospital Universitario Cruces, Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragini","family":"Jethra","sequence":"additional","affiliation":[{"name":"Advanced Immunotherapy and Cell Therapy, The Christie NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C","family":"Lorigan","sequence":"additional","affiliation":[{"name":"Melanoma Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK"},{"name":"The University of Manchester Faculty of Biology Medicine and Health, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6544-9218","authenticated-orcid":false,"given":"Kok Haw Jonathan","family":"Lim","sequence":"additional","affiliation":[{"name":"Advanced Immunotherapy and Cell Therapy, The Christie NHS Foundation Trust, Manchester, UK"},{"name":"Division of Cancer Sciences, The University of Manchester Faculty of Biology Medicine and Health, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Thistlethwaite","sequence":"additional","affiliation":[{"name":"Advanced Immunotherapy and Cell Therapy, The Christie NHS Foundation Trust, Manchester, UK"},{"name":"Division of Cancer Sciences, The University of Manchester Faculty of Biology Medicine and Health, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"2026040909152254000_14.4.e014378.1","unstructured":"Woyke E . FDA approves first tumour-infiltrating lymphocyte therapy for solid tumours. Nat Med 2024."},{"key":"2026040909152254000_14.4.e014378.2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00612"},{"key":"2026040909152254000_14.4.e014378.3","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1200\/JCO-25-00765","article-title":"Long-Term Efficacy and Safety of Lifileucel Tumor-Infiltrating Lymphocyte Cell Therapy in Patients With Advanced Melanoma: A 5-Year Analysis of the C-144-01 Study","volume":"43","author":"Medina","year":"2025","journal-title":"J Clin Oncol"},{"key":"2026040909152254000_14.4.e014378.4","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1158\/2159-8290.CD-23-1334","article-title":"Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors","volume":"14","author":"Schoenfeld","year":"2024","journal-title":"Cancer Discov"},{"key":"2026040909152254000_14.4.e014378.5","doi-asserted-by":"crossref","first-page":"100737","DOI":"10.1016\/j.iotech.2024.100737","article-title":"Solid tumour cellular therapy \u2014 principles of toxicity management","volume":"25","author":"Julve","year":"2025","journal-title":"Immuno-Oncol Technol"},{"key":"2026040909152254000_14.4.e014378.6","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2428"},{"key":"2026040909152254000_14.4.e014378.7","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200205000-00007"},{"key":"2026040909152254000_14.4.e014378.8","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200107000-00012"},{"key":"2026040909152254000_14.4.e014378.9","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.00.240"},{"key":"2026040909152254000_14.4.e014378.10","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-008735","article-title":"Expert consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy","volume":"12","author":"Betof Warner","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.11","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-010207","article-title":"Art of TIL immunotherapy: SITC\u2019s perspective on demystifying a complex treatment","volume":"13","author":"Turcotte","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.12","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2025-013420","article-title":"The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee","volume":"13","author":"Coukos","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.13","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.annonc.2025.04.001","article-title":"Safety of adoptive therapy with tumor-infiltrating lymphocytes and high-dose recombinant interleukin 2 in advanced cutaneous melanoma: a systematic review and meta-analysis","volume":"36","author":"Mart\u00edn-Lluesma","year":"2025","journal-title":"Ann Oncol"},{"key":"2026040909152254000_14.4.e014378.14","doi-asserted-by":"publisher","DOI":"10.1038\/ncponc0666"},{"key":"2026040909152254000_14.4.e014378.15","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-022-03287-1"},{"key":"2026040909152254000_14.4.e014378.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.12.018"},{"key":"2026040909152254000_14.4.e014378.17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.urols.2014.03.001","article-title":"Cyclophosphamide-induced intractable hemorrhagic cystitis treated with hyperbaric oxygenation and intravesical sodium hyaluronate","volume":"25","author":"Tsai","year":"2014","journal-title":"Urol Sci"},{"key":"2026040909152254000_14.4.e014378.18","unstructured":"FDA . Cyclophosphamide for injection, USP cyclophosphamide tablets, USP reference ID: 3110031 ed2012."},{"key":"2026040909152254000_14.4.e014378.19","doi-asserted-by":"crossref","first-page":"115741","DOI":"10.1016\/j.bcp.2023.115741","article-title":"Nucleoside-based anticancer drugs: Mechanism of action and drug resistance","volume":"215","author":"Hruba","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"2026040909152254000_14.4.e014378.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-018-0019-6"},{"key":"2026040909152254000_14.4.e014378.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-023-00221-y"},{"key":"2026040909152254000_14.4.e014378.22","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042617-053352"},{"key":"2026040909152254000_14.4.e014378.23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1991.9.4.694"},{"key":"2026040909152254000_14.4.e014378.24","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1200\/JCO.1988.6.4.669","article-title":"Influence of dose and duration of infusion of interleukin-2 on toxicity and immunomodulation","volume":"6","author":"Thompson","year":"1988","journal-title":"J Clin Oncol"},{"key":"2026040909152254000_14.4.e014378.25","doi-asserted-by":"crossref","DOI":"10.1186\/1479-5876-2-17","article-title":"Forecasting the cytokine storm following systemic interleukin (IL)-2 administration","volume":"2","author":"Panelli","year":"2004","journal-title":"J Transl Med"},{"key":"2026040909152254000_14.4.e014378.26","doi-asserted-by":"crossref","first-page":"157","DOI":"10.4049\/jimmunol.134.1.157","article-title":"In vivo administration of purified human interleukin 2. I. Half-life and immunologic effects of the Jurkat cell line-derived interleukin 2","volume":"134","author":"Lotze","year":"1985","journal-title":"J Immunol"},{"key":"2026040909152254000_14.4.e014378.27","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.4049\/jimmunol.135.4.2865","article-title":"In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2","volume":"135","author":"Lotze","year":"1985","journal-title":"J Immunol"},{"key":"2026040909152254000_14.4.e014378.28","doi-asserted-by":"publisher","DOI":"10.1038\/nri3191"},{"key":"2026040909152254000_14.4.e014378.29","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000157"},{"key":"2026040909152254000_14.4.e014378.30","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.5449"},{"key":"2026040909152254000_14.4.e014378.31","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200501000-00007"},{"key":"2026040909152254000_14.4.e014378.32","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1200\/JCO.2024.42.16_suppl.2549","article-title":"A first-in-human study of CRISPR\/Cas9-engineered tumor infiltrating lymphocytes (TILs) product GT316 as monotherapy in advanced solid tumors","volume":"42","author":"Guo","year":"2024","journal-title":"JCO"},{"key":"2026040909152254000_14.4.e014378.33","doi-asserted-by":"crossref","DOI":"10.1016\/j.iotech.2024.100728","article-title":"Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma","volume":"24","author":"K\u00f6nig","year":"2024","journal-title":"Immunooncol Technol"},{"key":"2026040909152254000_14.4.e014378.34","doi-asserted-by":"crossref","unstructured":"Jazaeri AA , Zsiros E , Amaria RN , et al . Safety and efficacy of adoptive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervical carcinoma. American Society of Clinical Oncology, 2019.","DOI":"10.1016\/j.ygyno.2018.04.274"},{"key":"2026040909152254000_14.4.e014378.35","doi-asserted-by":"crossref","first-page":"S914","DOI":"10.1016\/j.annonc.2025.08.2277","article-title":"1649P First real-world data for TIL therapy in patients with metastatic cutaneous melanoma","volume":"36","author":"Tak","year":"2025","journal-title":"Ann Oncol"},{"key":"2026040909152254000_14.4.e014378.36","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2025.08.2278","article-title":"1650P Real-world outcomes of tumor-infiltrating lymphocyte (TIL) therapy for metastatic melanoma patients in 2025","volume":"36","author":"Grynberg","year":"2025","journal-title":"Ann Oncol"},{"key":"2026040909152254000_14.4.e014378.37","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-0041"},{"key":"2026040909152254000_14.4.e014378.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01462-y"},{"key":"2026040909152254000_14.4.e014378.39","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0116"},{"key":"2026040909152254000_14.4.e014378.40","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.9093"},{"key":"2026040909152254000_14.4.e014378.41","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-005755","article-title":"Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study","volume":"10","author":"Chesney","year":"2022","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.42","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.46.6441"},{"key":"2026040909152254000_14.4.e014378.43","first-page":"A523","article-title":"492\u2005Phase 2 efficacy and safety of autologous tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab in immune checkpoint inhibitor-na\u00efve patients with advanced cancers","volume":"9(Suppl 2)","author":"O\u2019Malley","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.44","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0380"},{"key":"2026040909152254000_14.4.e014378.45","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s00262-019-02307-x","article-title":"Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2","volume":"68","author":"Nguyen","year":"2019","journal-title":"Cancer Immunol Immunother"},{"key":"2026040909152254000_14.4.e014378.46","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1879"},{"key":"2026040909152254000_14.4.e014378.47","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-000848","article-title":"Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up","volume":"8","author":"van den Berg","year":"2020","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.48","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210233"},{"key":"2026040909152254000_14.4.e014378.49","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003499","article-title":"Adoptive cell therapy with tumor-infiltrating lymphocytes supported by checkpoint inhibition across multiple solid cancer types","volume":"9","author":"Kverneland","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.50","doi-asserted-by":"crossref","DOI":"10.1186\/1479-5876-10-169","article-title":"Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients","volume":"10","author":"Ellebaek","year":"2012","journal-title":"J Transl Med"},{"key":"2026040909152254000_14.4.e014378.51","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz398"},{"key":"2026040909152254000_14.4.e014378.52","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/mc.23193","article-title":"Comprehensive single institute experience with melanoma TIL: Long term clinical results, toxicity profile, and prognostic factors of response","volume":"59","author":"Besser","year":"2020","journal-title":"Mol Carcinog"},{"key":"2026040909152254000_14.4.e014378.53","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2340\/1651-226X.2024.40495","article-title":"NIVO-TIL: combination anti-PD-1 therapy and adoptive T-cell transfer in untreated metastatic melanoma: an exploratory open-label phase I trial","volume":"63","author":"L\u2019Orphelin","year":"2024","journal-title":"AO"},{"key":"2026040909152254000_14.4.e014378.54","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1158\/1078-0432.CCR-24-4322","article-title":"Effective TIL Therapy for Patients with Checkpoint-Resistant Melanoma without Lymphodepleting Regimens Requires IFN\u03b1","volume":"31","author":"Verdegaal","year":"2025","journal-title":"Clin Cancer Res"},{"key":"2026040909152254000_14.4.e014378.55","doi-asserted-by":"crossref","DOI":"10.1172\/JCI157726","article-title":"Phase I study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer","volume":"132","author":"Huang","year":"2022","journal-title":"J Clin Invest"},{"key":"2026040909152254000_14.4.e014378.56","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-1171"},{"key":"2026040909152254000_14.4.e014378.57","doi-asserted-by":"crossref","DOI":"10.1016\/j.iotech.2024.100726","article-title":"Durable complete response after combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus (TILT-123) in a patient with metastatic mucosal melanoma","volume":"24","author":"Monberg","year":"2024","journal-title":"Immunooncol Technol"},{"key":"2026040909152254000_14.4.e014378.58","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1200\/JCO.1988.6.5.839","article-title":"Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study","volume":"6","author":"Topalian","year":"1988","journal-title":"JCO"},{"key":"2026040909152254000_14.4.e014378.59","doi-asserted-by":"crossref","DOI":"10.1093\/bjs\/znaf090","article-title":"Surgical considerations for tumour-infiltrating lymphocyte therapy in melanoma: results from a randomized phase III trial","volume":"112","author":"Tas","year":"2025","journal-title":"Br J Surg"},{"key":"2026040909152254000_14.4.e014378.60","doi-asserted-by":"crossref","first-page":"898","DOI":"10.3892\/etm.2012.498","article-title":"Adoptive cell therapy with autologous tumor-infiltrating lymphocytes and high-dose interleukin-2 for metastatic melanoma: The surgeon\u2019s perspective","volume":"3","author":"Zippel","year":"2012","journal-title":"Exp Ther Med"},{"key":"2026040909152254000_14.4.e014378.61","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.13689"},{"key":"2026040909152254000_14.4.e014378.62","doi-asserted-by":"crossref","DOI":"10.1007\/s12672-024-01410-5","article-title":"Advances and prospects in tumor infiltrating lymphocyte therapy","volume":"15","author":"Qiu","year":"2024","journal-title":"Discov Oncol"},{"key":"2026040909152254000_14.4.e014378.63","doi-asserted-by":"publisher","DOI":"10.1097\/01.cji.0000211321.07654.b8"},{"key":"2026040909152254000_14.4.e014378.64","first-page":"3967","article-title":"Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma","volume":"12","author":"Pillai","year":"2022","journal-title":"Am J Cancer Res"},{"key":"2026040909152254000_14.4.e014378.65","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1297"},{"key":"2026040909152254000_14.4.e014378.66","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.66.7220"},{"key":"2026040909152254000_14.4.e014378.67","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1994.12.7.1475"},{"key":"2026040909152254000_14.4.e014378.68","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2023.2290900","article-title":"LTX-315 and adoptive cell therapy using tumor-infiltrating lymphocytes generate tumor specific T cells in patients with metastatic soft tissue sarcoma","volume":"13","author":"Nielsen","year":"2024","journal-title":"Oncoimmunology"},{"key":"2026040909152254000_14.4.e014378.69","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-006822","article-title":"Efficacy and safety of autologous tumor-infiltrating lymphocytes in recurrent or refractory ovarian cancer, colorectal cancer, and pancreatic ductal adenocarcinoma","volume":"12","author":"Amaria","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.70","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-001743","article-title":"Comparison of non-myeloablative lymphodepleting preconditioning regimens in patients undergoing adoptive T cell therapy","volume":"9","author":"Nissani","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.71","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2025.2546402","article-title":"Lymphodepletion, tumor-infiltrating lymphocytes, and high versus low dose IL-2 followed by pembrolizumab in patients with metastatic melanoma","volume":"14","author":"Hasanov","year":"2025","journal-title":"Oncoimmunology"},{"key":"2026040909152254000_14.4.e014378.72","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jtct.2025.12.009","article-title":"Safety and Efficacy of Tumor-Infiltrating Lymphocyte Therapy with Reduced-Dose Lymphodepleting Conditioning in High-Risk Metastatic Melanoma Patients","volume":"32","author":"Karapetyan","year":"2026","journal-title":"Transplant Cell Ther"},{"key":"2026040909152254000_14.4.e014378.73","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-011-1182-4"},{"key":"2026040909152254000_14.4.e014378.74","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2025.08.2280","article-title":"1652P A phase I clinical trial of autologous tumor-infiltrating lymphocytes FAST-TIL (HS-IT101) with low-dose IL-2 for the treatment of advanced solid tumors: Subgroup analysis of melanoma","volume":"36","author":"Jiang","year":"2025","journal-title":"Ann Oncol"},{"key":"2026040909152254000_14.4.e014378.75","first-page":"212","article-title":"The Toxicity and Benefit of Various Dosing Strategies for Interleukin-2 in Metastatic Melanoma and Renal Cell Carcinoma","volume":"6","author":"Pachella","year":"2015","journal-title":"J Adv Pract Oncol"},{"key":"2026040909152254000_14.4.e014378.76","doi-asserted-by":"crossref","first-page":"360","DOI":"10.7150\/jca.2.360","article-title":"Adoptive Cell Therapy for Patients with Melanoma","volume":"2","author":"Dudley","year":"2011","journal-title":"J Cancer"},{"key":"2026040909152254000_14.4.e014378.77","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1177"},{"key":"2026040909152254000_14.4.e014378.78","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-008640","article-title":"Biomarkers for response to TIL therapy: a comprehensive review","volume":"12","author":"Albarr\u00e1n Fern\u00e1ndez","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.79","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.17.2627"},{"key":"2026040909152254000_14.4.e014378.80","doi-asserted-by":"crossref","first-page":"S395","DOI":"10.1016\/j.jtho.2022.07.682","article-title":"EP08.01-110 Trial in Progress: A Phase 2 Multicenter Study (IOV-LUN-202) of Autologous Tumor-infiltrating Lymphocyte (TIL) Cell Therapy (LN-145) in mNSCLC","volume":"17","author":"Chesney","year":"2022","journal-title":"J Thorac Oncol"},{"key":"2026040909152254000_14.4.e014378.81","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198812223192527"},{"key":"2026040909152254000_14.4.e014378.82","doi-asserted-by":"crossref","first-page":"100140","DOI":"10.1016\/j.iotech.2022.100140","article-title":"35MO Number of IL-2 doses and clinical outcomes of tumor-infiltrating lymphocyte (TIL) cell therapy: Post hoc analysis of the C-144-01 trial of lifileucel in patients with advanced melanoma","volume":"16","author":"Hassel","year":"2022","journal-title":"Immuno-Oncol Technol"},{"key":"2026040909152254000_14.4.e014378.83","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1182\/bloodadvances.2023011492","article-title":"Bendamustine lymphodepletion before axicabtagene ciloleucel is safe and associates with reduced inflammatory cytokines","volume":"8","author":"Ghilardi","year":"2024","journal-title":"Blood Adv"},{"key":"2026040909152254000_14.4.e014378.84","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-008975","article-title":"Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma","volume":"12","author":"Bharadwaj","year":"2024","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.85","doi-asserted-by":"crossref","first-page":"152145","DOI":"10.1016\/j.bbrc.2025.152145","article-title":"Anti-TNFR2 antibody and HMGN1 combined with TIL cell therapy inhibits colorectal cancer progression by enhancing immune response","volume":"775","author":"Lv","year":"2025","journal-title":"Biochem Biophys Res Commun"},{"key":"2026040909152254000_14.4.e014378.86","doi-asserted-by":"crossref","first-page":"100332","DOI":"10.1016\/j.jbo.2020.100332","article-title":"Adoptive transfer of TILs plus anti-PD1 therapy: An alternative combination therapy for treating metastatic osteosarcoma","volume":"25","author":"Wang","year":"2020","journal-title":"J Bone Oncol"},{"key":"2026040909152254000_14.4.e014378.87","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1200\/JCO.2024.42.16_suppl.2552","article-title":"IOV-3001, a modified interleukin-2 fusion protein, for potential use in tumor-infiltrating lymphocyte cell therapy regimens","volume":"42","author":"Abelson","year":"2024","journal-title":"JCO"},{"key":"2026040909152254000_14.4.e014378.88","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2025.102257","article-title":"Coupling IL-2 with IL-10 to mitigate toxicity and enhance antitumor immunity","volume":"6","author":"Ahn","year":"2025","journal-title":"Cell Rep Med"},{"key":"2026040909152254000_14.4.e014378.89","doi-asserted-by":"crossref","first-page":"1537466","DOI":"10.3389\/fimmu.2025.1537466","article-title":"AWT020: a novel fusion protein harnessing PD-1 blockade and selective IL-2 Cis-activation for enhanced anti-tumor immunity and diminished toxicity","volume":"16","author":"Ye","year":"2025","journal-title":"Front Immunol"},{"key":"2026040909152254000_14.4.e014378.90","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-010831","article-title":"Combinatorial treatment with upadacitinib abrogates systemic toxicity of a tumor-targeted IL-2 fusion protein","volume":"13","author":"Rotta","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026040909152254000_14.4.e014378.91","doi-asserted-by":"crossref","first-page":"4756","DOI":"10.1200\/JCO.23.00172","article-title":"Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results","volume":"41","author":"Diab","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026040909152254000_14.4.e014378.92","unstructured":"Gerald F , Hui G , Siqing F , et al . 481 Phase 1\/2 study of THOR-707 (SAR444245), a pegylated recombinant non-alpha IL-2, as monotherapy and in combination with pembrolizumab or cetuximab in patients (pts) with advanced solid tumors. J Immunother Cancer 2021;9."},{"key":"2026040909152254000_14.4.e014378.93","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2024.101747","article-title":"A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2R\u03b1 strengthens T cell-mediated anti-tumor therapies","volume":"5","author":"Wu","year":"2024","journal-title":"Cell Rep Med"},{"key":"2026040909152254000_14.4.e014378.94","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abg6986","article-title":"A human orthogonal IL-2 and IL-2R\u03b2 system enhances CAR T cell expansion and antitumor activity in a murine model of leukemia","volume":"13","author":"Zhang","year":"2021","journal-title":"Sci Transl Med"},{"key":"2026040909152254000_14.4.e014378.95","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar3246"},{"key":"2026040909152254000_14.4.e014378.96","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21217814","article-title":"Investigation of the Impact from IL-2, IL-7, and IL-15 on the Growth and Signaling of Activated CD4+ T Cells","volume":"21","author":"Coppola","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026040909152254000_14.4.e014378.97","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-009-0573-0"},{"key":"2026040909152254000_14.4.e014378.98","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-019-0643-y"},{"key":"2026040909152254000_14.4.e014378.99","doi-asserted-by":"crossref","unstructured":"Li N , Wu D , Fang Y , et al . Autologous tumor-infiltrating lymphocytes (HS-IT101) with low-dose lymphodepletion and IL-2 infusion for the treatment of advanced solid tumors: A phase I clinical trial. JCO 2025;43. doi:10.1200\/JCO.2025.43.16_suppl.TPS2674","DOI":"10.1200\/JCO.2025.43.16_suppl.TPS2674"},{"key":"2026040909152254000_14.4.e014378.100","doi-asserted-by":"crossref","unstructured":"Palmer D , Webber B , Patel Y , et al . 333\u2005Targeting the apical intracellular checkpoint cish unleashes T cell neoantigen reactivity and effector program. J Immunother Cancer 2020. doi:10.1136\/jitc-2020-SITC2020.0333","DOI":"10.1136\/jitc-2020-SITC2020.0333"},{"key":"2026040909152254000_14.4.e014378.101","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.omto.2022.01.004","article-title":"Highly efficient PD-1-targeted CRISPR-Cas9 for tumor-infiltrating lymphocyte-based adoptive T cell therapy","volume":"24","author":"Chamberlain","year":"2022","journal-title":"Mol Ther Oncolytics"},{"key":"2026040909152254000_14.4.e014378.102","doi-asserted-by":"crossref","first-page":"4104","DOI":"10.4049\/jimmunol.150.9.4104","article-title":"Functional and molecular characterization of tumor-infiltrating lymphocytes transduced with tumor necrosis factor-alpha cDNA for the gene therapy of cancer in humans","volume":"150","author":"Hwu","year":"1993","journal-title":"J Immunol"},{"key":"2026040909152254000_14.4.e014378.103","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1006\/cimm.1994.1189","article-title":"Upregulation of Tumor Necrosis Factor-\u03b1 Production by Retrovirally Transduced Human Tumor-Infiltrating Lymphocytes Using trans-Retinoic Acid","volume":"156","author":"Treisman","year":"1994","journal-title":"Cell Immunol"},{"key":"2026040909152254000_14.4.e014378.104","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1158\/1538-7445.AM2025-3192","article-title":"Abstract 3192: GT316: a next-generation TIL therapy identified through genome-wide CRISPR screening with promising efficacy in advanced solid tumors","volume":"85","author":"Sun","year":"2025","journal-title":"Cancer Res"},{"key":"2026040909152254000_14.4.e014378.105","doi-asserted-by":"crossref","first-page":"9515","DOI":"10.1200\/JCO.2024.42.16_suppl.9515","article-title":"OBX-115, an interleukin 2 (IL2)-sparing engineered tumor-infiltrating lymphocyte (TIL) cell therapy, in patients (pts) with immune checkpoint inhibitor (ICI)-resistant unresectable or metastatic melanoma","volume":"42","author":"Amaria","year":"2024","journal-title":"JCO"},{"key":"2026040909152254000_14.4.e014378.106","doi-asserted-by":"crossref","first-page":"9519","DOI":"10.1200\/JCO.2025.43.16_suppl.9519","article-title":"OBX-115 engineered tumor-infiltrating lymphocytes (TIL) with regulatable membrane-bound IL15 (mbIL15): Translational data from a single-center phase 1 trial in patients (pts) with immune checkpoint inhibitor (ICI)\u2013resistant advanced melanoma","volume":"43","author":"Amaria","year":"2025","journal-title":"JCO"},{"key":"2026040909152254000_14.4.e014378.107","doi-asserted-by":"crossref","first-page":"S915","DOI":"10.1016\/j.annonc.2025.08.2281","article-title":"1653P CRISPR-PD1 modified tumor infiltrating lymphocytes for adoptive therapy for patients with metastatic melanoma","volume":"36","author":"Sohlin","year":"2025","journal-title":"Ann Oncol"},{"key":"2026040909152254000_14.4.e014378.108","doi-asserted-by":"crossref","first-page":"11","DOI":"10.46989\/001c.115793","article-title":"Outpatient CAR T-Cell Therapy as Standard of Care: Current Perspectives and Considerations","volume":"6","author":"Gatwood","year":"2024","journal-title":"Clin Hematol Int"},{"key":"2026040909152254000_14.4.e014378.109","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-9-138"},{"key":"2026040909152254000_14.4.e014378.110","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2023.41.16_suppl.e13626","article-title":"Early detection of CRS after CAR-T therapy using wearable monitoring devices: Preliminary results in relapsed\/refractory multiple myeloma (RRMM)","volume":"41","author":"Rajeeve","year":"2023","journal-title":"JCO"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-014378","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T16:15:43Z","timestamp":1775751343000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-014378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":110,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,9]]},"published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1136\/jitc-2025-014378"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-014378","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]}}}