{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:02:26Z","timestamp":1777006946438,"version":"3.51.4"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Uveal melanoma (UM) is a rare intraocular malignancy with limited systemic treatment options and poor outcomes once metastatic. Tebentafusp, an ImmTAC (Immune-mobilizing monoclonal T-cell receptor Against Cancer) targeting gp100 in HLA-A*02:01\u2013positive patients, has improved survival, although durable responses remain uncommon. Radiotherapy (RT) has been shown to induce immunogenic cell death and to modulate antitumor immune responses, supporting a potential synergistic interaction with systemic immunomodulatory therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We described a 39-year-old woman with localized UM initially treated with proton therapy (60 Gy in four fractions), who developed liver and hilar adenopathies metastases seven years later. After confirmation of metastatic melanoma and HLA-A*02:01 positivity, tebentafusp was started and well tolerated. Following four months of therapy, imaging revealed oligoprogression in a hilar adenopathy, while hepatic lesions remained stable. Stereotactic body radiotherapy (SBRT; 30 Gy in 10 fractions) was delivered to the nodal site while tebentafusp was continued. Subsequent MRI at nine months demonstrated partial response across all lesions. The patient has maintained disease control for an additional 35 months, with excellent quality of life (ECOG PS 0).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case illustrates a durable systemic response after combined tebentafusp and SBRT, suggesting a synergistic interaction between ImmTAC-mediated T-cell activation and radiation-induced immunogenic modulation. Local RT may enhance antigen release and T-cell recruitment, amplifying tebentafusp efficacy and inducing abscopal-like effects. Prospective studies are warranted to evaluate this combination and identify biomarkers predictive of response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1749363","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:30:36Z","timestamp":1777005036000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Long-term response to multimodal treatment in metastatic uveal melanoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Francesca","family":"Rifaldi","sequence":"first","affiliation":[{"name":"Melanoma Medical Oncology Unit, Department of Medical Oncology ed Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]},{"name":"Department of Oncology, Comprehensive Cancer Center, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo Foundation","place":["Pavia, Italy"]},{"name":"Department of Internal Medicine and Medical Therapy, University of Pavia","place":["Pavia, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Angi","sequence":"additional","affiliation":[{"name":"Ocular Oncology Unit, Department of Surgical Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Leone","sequence":"additional","affiliation":[{"name":"Melanoma Medical Oncology Unit, Department of Medical Oncology ed Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"De Ponti","sequence":"additional","affiliation":[{"name":"Melanoma Medical Oncology Unit, Department of Medical Oncology ed Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Vaiani","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Spagnoletti","sequence":"additional","affiliation":[{"name":"Melanoma Medical Oncology Unit, Department of Medical Oncology ed Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Indini","sequence":"additional","affiliation":[{"name":"Melanoma Medical Oncology Unit, Department of Medical Oncology ed Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Del Vecchio","sequence":"additional","affiliation":[{"name":"Melanoma Medical Oncology Unit, Department of Medical Oncology ed Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenza Alessia","family":"Di Guardo","sequence":"additional","affiliation":[{"name":"Melanoma Medical Oncology Unit, Department of Medical Oncology ed Hematology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori","place":["Milan, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2012.126","article-title":"Progress in the management of patients with uveal melanoma. 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