{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:12:14Z","timestamp":1790683934282,"version":"4.1.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"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:p>Sequential or concurrent thoracic radiotherapy and immune checkpoint inhibitors (ICIs) increase the risk of severe overlapping pulmonary toxicity. Progressive pneumonitis after thoracic radiotherapy and ICI exposure remains a clinically challenging condition, particularly when it shows an inadequate response to systemic corticosteroid therapy. We report a 65-year-old man with esophageal cancer who developed progressive radiation pneumonitis with possible immune-mediated contribution after pembrolizumab therapy and thoracic radiotherapy. Despite moderate-dose systemic corticosteroid therapy, he experienced rapid clinical and radiographic deterioration. Laboratory evaluation showed a hyper-inflammatory phenotype, with elevated interleukin-6, ferritin, and C-reactive protein levels. Based on this hyper-inflammatory profile, we initiated a hypothesis-driven salvage regimen comprising corticosteroid therapy, the JAK inhibitor tofacitinib, and nintedanib. This intervention was associated with symptomatic improvement, declining inflammatory biomarkers, and near-complete radiographic resolution. No clinically evident severe treatment-related adverse events were observed during follow-up. Transient diarrhea occurred after nintedanib initiation and improved after dose reduction. This case suggests that biologically rational integration of JAK inhibition and anti-fibrotic therapy may be considered as a hypothesis-driven salvage approach in selected patients with progressive radiation pneumonitis with possible immune-mediated contribution after inadequate response to systemic corticosteroid therapy.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1913167","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:55:46Z","timestamp":1786514146000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypothesis-driven salvage therapy with corticosteroids, tofacitinib, and nintedanib for progressive radiation pneumonitis with possible immune-mediated contribution: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Xi","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Respiratory 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