{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T05:04:32Z","timestamp":1774587872379,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["F30 CA 243307, R01 CA175061, R01 CA208514"],"award-info":[{"award-number":["F30 CA 243307, R01 CA175061, R01 CA208514"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM008716"],"award-info":[{"award-number":["T32 GM008716"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Autoimmune toxicities, while common following treatment with cancer immunotherapies, are not well-characterized in patients treated with BRAF\/MEK inhibitors. Emerging data suggest that autoimmune effects may be linked with superior responses to both treatment modalities; however, there is little evidence describing mechanisms of immune-related toxicity for patients on BRAF\/MEK inhibitors. Here we describe the experience of a 59-year-old HLA-A2, A29, B27-positive male with recurrent\/metastatic melanoma. After progression on checkpoint inhibitor therapy, he was treated with dabrafenib\/trametinib followed by encorafenib\/binimetinib, which were well-tolerated and resulted in a complete response. Eighteen months into BRAF\/MEK inhibitor therapy, and three months after initially finding a complete response, he developed a series of sudden-onset, severe toxicities: namely, bilateral panuveitis, cytopenias, joint pain, skin rash, hypercalcemia, and interstitial nephritis, which led to BRAF\/MEKi cessation. Immunological analyses revealed induction of a peripheral type-17 cytokine signature characterized by high IL-23, IL-6, IL-10, IL-17A\/F, IL-1\u03b2, and IL-21 among other cytokines in plasma corresponding with the height of symptoms. These findings highlight a novel instance of delayed autoimmune-like reaction to BRAF\/MEK inhibition and identify a possible role for Th\/Tc17 activation in their pathogenesis thus warranting future clinical and immunological characterization.<\/jats:p>","DOI":"10.3389\/fonc.2022.836845","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T10:57:05Z","timestamp":1648724225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Case Report: Delayed Onset Multi-Organ Toxicities in a Melanoma Patient Achieving Complete Response to BRAF\/MEK Inhibition"],"prefix":"10.3389","volume":"12","author":[{"given":"Hannah M.","family":"Knochelmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael 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