{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:04:11Z","timestamp":1785855851021,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,26]]},"group-title":"Allergy and Immunology","reference-count":10,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but commonly cause immune-related adverse events (irAEs), whether administered as monotherapy or in combination with other oncological agents. We present the first reported case of ICI-induced granulomatous sialadenitis in a male patient in his mid-fifties with BRAF-V600E-mutated papillary thyroid carcinoma who received sequential treatment with BRAF\/MEK inhibitors followed by pembrolizumab. The patient experienced acute-onset severe xerostomia and salivary hypofunction, prompting ICI cessation and salivary gland biopsy. Integrative analysis using histology, single-cell RNA sequencing, and spatial transcriptomics revealed macrophage- and T-cell-mediated epithelial damage driven by epithelial senescence and Th1-polarized inflammation. Corticosteroid therapy reduced granuloma burden and improved salivary flow rates and tissue architecture; however, extensive fibrosis persisted despite treatment. These findings underscore the critical importance of early irAE recognition and intervention to preserve glandular function and enable continuation of cancer therapy.<\/jats:p>","DOI":"10.64898\/2026.01.21.26344113","type":"posted-content","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T23:50:17Z","timestamp":1769471417000},"source":"Crossref","is-referenced-by-count":1,"title":["ICI-induced Granulomatous Sialadenitis is Responsive to Prednisone"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2904-7107","authenticated-orcid":false,"given":"Rachel J.","family":"Kulchar","sequence":"first","affiliation":[{"name":"Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"},{"name":"Sj\u00f6gren\u2019s Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"},{"name":"School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA"},{"name":"Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amara","family":"Ogbonnaya-Whittlesey","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Beach","sequence":"additional","affiliation":[{"name":"Sj\u00f6gren\u2019s Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohreh","family":"Khavandgar","sequence":"additional","affiliation":[{"name":"Sj\u00f6gren\u2019s Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Pelayo","sequence":"additional","affiliation":[{"name":"Sj\u00f6gren\u2019s Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Kleiner","sequence":"additional","affiliation":[{"name":"Sj\u00f6gren\u2019s Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"},{"name":"Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Perez","sequence":"additional","affiliation":[{"name":"Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"},{"name":"Sj\u00f6gren\u2019s Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Martin","sequence":"additional","affiliation":[{"name":"Genomics and Computational Biology Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Burbelo","sequence":"additional","affiliation":[{"name":"Sj\u00f6gren\u2019s Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"},{"name":"AAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Chiorini","sequence":"additional","affiliation":[{"name":"Sj\u00f6gren\u2019s Disease Clinic, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"},{"name":"AAV Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-7520","authenticated-orcid":false,"given":"Paul","family":"Boutros","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Wilmot Ball","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, & Metabolism, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Boudadi","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine, Johns Hopkins Kimmel Cancer Center, 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