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However, the underlying tissue-level mechanisms remain poorly understood. To uncover cell functions and spatial organization surrounding ONJ lesions, imaging mass cytometry is used to profile lesions at single-cell resolution across epithelial, stromal, and vascular regions. Widespread immune infiltration is observed, with regulatory T cells, M2-like macrophages, exhausted T cells, and natural killer cells shifting from dispersed to clustered spatial patterns, indicating altered immune organization. Epithelial regions show reduced epithelial marker expression and disrupted architecture despite elevated proliferation-related markers, while fibroblasts and endothelial cells display signs of activation. Functional profiling reveals concurrent proliferative, apoptotic, and stress-associated signatures across multiple cell populations. 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