{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:43:50Z","timestamp":1779903830747,"version":"3.53.1"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["Ricerca Corrente 2018\u20132025"],"award-info":[{"award-number":["Ricerca Corrente 2018\u20132025"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: BRAF and\/or MEK inhibitors are widely used for patients with BRAF-mutated melanoma, but no biomarkers of response or resistance are currently available. Besides adverse events in different organs, target therapy with BRAF and\/or MEK inhibitors may induce the onset of immune-related adverse events (irAEs) that have been considered as possible biomarkers of good prognosis in patients with melanoma. Methods: To investigate this aspect, we analyzed the occurrence of irAEs in a cohort of 158 patients treated with BRAF and MEK inhibitors. We also analyzed by flow cytometry the subsets of circulating immune cells in the patients who developed irAEs and matched controls. Results: We found that irAEs occurred in 3 out of 101 patients (3%) who experienced adverse events. These three patients did not exhibit any specific clinical features or circulating immune cell subtypes that could be associated with a positive response to treatment. However, the onset of toxicity in the entire patient cohort was associated with longer progression-free survival. Notably, the frequency of circulating follicular helper T cells increased in all examined patients during the first two months of treatment. Conclusions: The small sample size prevents us from determining whether irAEs are effectively caused by BRAF\/MEK inhibitors or if they are a random event. Additionally, we cannot conclude whether irAEs are related to a better outcome. Nevertheless, we note that BRAF\/MEK inhibition may alter the composition of circulating immune cells in melanoma patients. This aspect should be investigated further before proposing combinations of target therapies and immunotherapies.<\/jats:p>","DOI":"10.3390\/cancers18071072","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:36:40Z","timestamp":1774532200000},"page":"1072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune-Related Adverse Events in Patients with Melanoma Treated with B-RAF\/MEK Target Therapy: Occurrence and Circulating Immune Cell Analysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Alessia","family":"Capone","sequence":"first","affiliation":[{"name":"Molecular Neuroimmunology Laboratory, IRCCS Santa Lucia Foundation, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3350-1210","authenticated-orcid":false,"given":"Maria Luigia","family":"Carbone","sequence":"additional","affiliation":[{"name":"Experimental Immunology Laboratory, IDI-IRCCS, 00167 Rome, Italy"},{"name":"Clinical Trial Center, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-5347","authenticated-orcid":false,"given":"Simona","family":"Mastroeni","sequence":"additional","affiliation":[{"name":"National Centre for Disease Prevention and Health Promotion, Italian National Institute of Health, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-8753","authenticated-orcid":false,"given":"Francesca Romana","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Department of Oncology and Dermato Oncology, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Verkhovskaia","sequence":"additional","affiliation":[{"name":"Department of Oncology and Dermato Oncology, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Morese","sequence":"additional","affiliation":[{"name":"Department of Oncology and Dermato Oncology, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidia","family":"Melo","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Unit, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"D\u2019Atri","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"De Galitiis","sequence":"additional","affiliation":[{"name":"Department of Oncology and Dermato Oncology, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9679-4711","authenticated-orcid":false,"given":"Rosa","family":"Falcone","sequence":"additional","affiliation":[{"name":"Department of Oncology and Dermato Oncology, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Fortes","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Unit, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-2422","authenticated-orcid":false,"given":"Elisabetta","family":"Volpe","sequence":"additional","affiliation":[{"name":"Molecular Neuroimmunology Laboratory, IRCCS Santa Lucia Foundation, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-8914","authenticated-orcid":false,"given":"Cristina Maria","family":"Failla","sequence":"additional","affiliation":[{"name":"Experimental Immunology Laboratory, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1001\/jama.2025.13074","article-title":"Cutaneous Melanoma: A Review","volume":"334","author":"Joshi","year":"2025","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Imani, S., Roozitalab, G., Emadi, M., Moradi, A., Behzadi, P., and Jabbarzadeh Kaboli, P. 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