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Abstract

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.

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