{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:53:21Z","timestamp":1785405201465,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mayo Clinic Comprehensive Cancer Center","award":["P30 CA015083"],"award-info":[{"award-number":["P30 CA015083"]}]},{"award":["P30 CA015083"],"award-info":[{"award-number":["P30 CA015083"]}],"id":[{"id":"https:\/\/ror.org\/012wxv498","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background\/Objectives: Tumor-infiltrating lymphocyte (TIL) therapy is an important option for patients with metastatic melanoma progressing after standard systemic therapy, but real-world data on treatment delivery, toxicity monitoring, and immune recovery remain limited. We evaluated clinical outcomes, treatment tolerance, immune reconstitution, and cardiac biomarker dynamics across three Mayo Clinic sites. Methods: We retrospectively analyzed adults with metastatic melanoma who received lymphodepleting chemotherapy followed by TIL infusion and high-dose interleukin-2 (IL-2) between April 2024 and December 2025. Clinical outcomes, treatment delivery, and adverse events were assessed. Longitudinal immune monitoring included CD4 and CD8 T-cell counts, CD4:CD8 ratio, and immunoglobulin G (IgG) at baseline and follow-up. In a prespecified cardiac sub-cohort, high-sensitivity troponin (hs-Tn) was measured during IL-2 administration to evaluate associations with cardiac events and IL-2 interruption. Results: Thirty-six patients underwent TIL infusion. The objective response rate was 50.0%, including complete responses in 13.9%, and the disease control rate was 72.2%. Median progression-free survival was 3.61 months, and median overall survival was 12.94 months. M1d disease was associated with inferior overall survival on univariable analysis (HR 6.55, 95% CI 2.03\u201321.17; p = 0.002), with attenuation after multivariable adjustment. Receipt of \u22653 IL-2 doses was associated with longer overall survival on univariable analysis (HR 0.20, 95% CI 0.06\u20130.64; p = 0.007), but this association also attenuated after adjustment. Longitudinal immune monitoring demonstrated persistent CD4 lymphopenia through 6 months, sustained inversion of the CD4:CD8 ratio, and declining IgG at months 3 and 6. In the cardiac sub-cohort (24 patients; 87 IL-2 doses), post-dose hs-Tn \u226515 ng\/L was associated with clinically significant cardiac events (OR 9.6, 95% CI 1.5\u201360.6; p = 0.016) and IL-2 interruption (OR 3.4, 95% CI 1.1\u201310.7; p = 0.036). For cardiac events, hs-Tn \u226515 ng\/L had 100% sensitivity and 100% negative predictive value. Conclusions: In routine practice, TIL therapy was feasible and active in metastatic melanoma. M1d disease identified a subgroup with poor survival, peri-dose hs-Tn showed promise as a tool to support safer IL-2 delivery, and prolonged CD4 suppression with IgG decline suggests that recovery after TIL therapy extends beyond initial hematologic reconstitution. These findings support prospective validation of biomarker-guided IL-2 monitoring and extended post-treatment immune surveillance.<\/jats:p>","DOI":"10.3390\/curroncol33070379","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:37:17Z","timestamp":1782279437000},"page":"379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Tumor-Infiltrating Lymphocyte Therapy for Metastatic Melanoma: Treatment Delivery, Immune Reconstitution, and Cardiac Monitoring During High-Dose IL-2"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3038-0780","authenticated-orcid":false,"given":"Mohamed A.","family":"Aboelatta","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8668-6741","authenticated-orcid":false,"given":"Jabra","family":"Zarka","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8323-9516","authenticated-orcid":false,"given":"Nika","family":"Tchatchua","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noureldin A.","family":"Aboelatta","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2912-443X","authenticated-orcid":false,"given":"Jeffrey E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8005-1072","authenticated-orcid":false,"given":"James W.","family":"Jakub","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9797-142X","authenticated-orcid":false,"given":"Justin","family":"Desroches","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Wilson-Miller","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5491-7880","authenticated-orcid":false,"given":"Anthony","family":"Tabiim","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-5055","authenticated-orcid":false,"given":"Deepti","family":"Behl","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7488-4767","authenticated-orcid":false,"given":"Heather N.","family":"Montane","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Kottschade","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3950-3305","authenticated-orcid":false,"given":"Anastasios","family":"Dimou","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Block","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth I.","family":"Heath","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bently","family":"Doonan","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Seetharam","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian R.","family":"Molina","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-2729","authenticated-orcid":false,"given":"Jonathan E.","family":"Charnin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Gill","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-3488","authenticated-orcid":false,"given":"Binav","family":"Baral","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetomir N.","family":"Markovic","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9114-8945","authenticated-orcid":false,"given":"Arkadiusz Z.","family":"Dudek","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104276","DOI":"10.1016\/j.critrevonc.2024.104276","article-title":"The treatment of advanced melanoma: Current approaches and new challenges","volume":"196","author":"Boutros","year":"2024","journal-title":"Crit. 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