{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:06:21Z","timestamp":1790892381166,"version":"4.1.0"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"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. Oncol."],"abstract":"<jats:p>Nivolumab, an anti-programmed death-1 (PD-1) receptor monoclonal antibody, has proven effective in treating platinum-resistant metastatic head and neck squamous cell carcinoma. Immune-related adverse events (irAEs) are well-known complications of PD-1 inhibitors. Meanwhile, cytokine release syndrome (CRS), a life-threatening immune-related adverse event, rarely develops due to nivolumab monotherapy. Here, we report a case of a 65-year-old man with squamous cell head and neck carcinoma of an occult primary origin who developed nivolumab-associated late-onset CRS that recurred. The patient was admitted with symptoms of fatigue, fever, hypotension, and respiratory distress. The diagnosis of CRS was supported by the elevated serum levels of interleukin-6 and ferritin, and the patient responded well to high-dose methylprednisolone. CRS recurred during steroid tapering, coinciding with an increased tumor burden; however, it was successfully managed with increased steroid dosing. Early detection and treatment with steroids are essential for the management of CRS.<\/jats:p>","DOI":"10.3389\/fonc.2025.1508682","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T06:50:22Z","timestamp":1738911022000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Late-onset and relapsed cytokine release syndrome after nivolumab treatment in a patient with head and neck squamous cell carcinoma: a case report"],"prefix":"10.3389","volume":"15","author":[{"given":"Tomoyuki","family":"Otsuka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Kojitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumio","family":"Imamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Fukutake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Nishio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"B1","unstructured":"National Comprehensive Cancer Network clinical practice guidelines in oncology\n          \n          \n          Head and neck cancers\n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00557","article-title":"Immune checkpoint inhibitor-related cytokine release syndrome: Analysis of WHO global pharmacovigilance database","volume":"11","author":"Ceschi","year":"2020","journal-title":"Front Pharmacol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.medin.2019.01.009","article-title":"Cytokine release syndrome. Reviewing a new entity in the intensive care unit","volume":"43","author":"Garc\u00eda Roche","year":"2019","journal-title":"Med Intensiva (Engl Ed)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Shimabukuro-Vornhagen","year":"2018","journal-title":"J Immunother Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.807050","article-title":"Cytokine release syndrome in cancer patients receiving immune checkpoint inhibitors: A case series of 25 patients and review of the literature","volume":"13","author":"Tay","year":"2022","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2021.0037","article-title":"Ferritin as a diagnostic, differential diagnostic, and prognostic marker for immune-related adverse events","volume":"18","author":"Zhang","year":"2021","journal-title":"Cancer Biol Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1172\/jci.insight.59125","article-title":"Clinical implications of monitoring nivolumab immunokinetics in non-small cell lung cancer patients","volume":"3","author":"Osa","year":"2018","journal-title":"JCI Insight"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1172\/JCI35180","article-title":"The anticancer immune response: indispensable for therapeutic success","volume":"118","author":"Zitvogel","year":"2008","journal-title":"J Clin Invest"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.02.011","article-title":"The association between tumor burden and severe immune-related adverse events in non-small cell lung cancer patients responding to immune-checkpoint inhibitor treatment","volume":"130","author":"Sakata","year":"2019","journal-title":"Lung Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2022.07.001","article-title":"Cytokine release syndrome and sepsis: Analogous clinical syndromes with distinct causes and challenges in management","volume":"36","author":"Athale","year":"2022","journal-title":"Infect Dis Clin North Am"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1190379","article-title":"Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures","volume":"14","author":"Shah","year":"2023","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01992","article-title":"Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO guideline","volume":"39","author":"Santomasso","year":"2021","journal-title":"J Clin Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1508682\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T06:50:25Z","timestamp":1738911025000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1508682\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":12,"alternative-id":["10.3389\/fonc.2025.1508682"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1508682","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,7]]},"article-number":"1508682"}}