{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T15:23:14Z","timestamp":1781018594811,"version":"3.54.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"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><jats:title>Purpose<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced malignancy but can induce immune-related adverse events (irAE). The mechanisms behind these sporadic and sometimes life-threatening irAEs remain largely unexplored. Here, we present a case report and in-depth molecular analysis of an erythema nodosum (EN) like irAE occurring in a melanoma patient with isolated brain metastasis, aiming to explore the potential mechanism of this irAE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed RNA and T cell receptor (TCR) sequencing on the patient\u2019s resected brain metastasis and biopsy of EN-like irAE. Single cell RNA\/TCR sequencing was conducted on the patient\u2019s peripheral blood mononuclear cells (PBMC) at baseline, 3 weeks after ipilimumab and nivolumab combination therapy, during EN toxicity and after resolution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The site of EN-like irAE showed a distinct accumulation of pro-inflammatory immune cells, accompanied by the upregulation of inflammatory and interferon response signatures. In addition, clonal expansion and activation of irAE-associated CD8 T cells and upregulation of monocyte-specific interferon signatures occurred concurrently with irAE onset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The unique immune landscape at the EN-like irAE could indicate that this irAE is distinct from anti-tumor immune and analogous non-ICI autoimmune milieus. Our data also suggests that systemic immune activation induced by ICI treatment, as reflected in PBMC, may help monitor the patient\u2019s treatment response and access irAE risk.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1542499","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T07:05:01Z","timestamp":1741849501000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular analysis of immune checkpoint inhibitor associated erythema nodosum-like toxicity"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaopeng","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret L.","family":"Axelrod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula 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