By combining immunohistochemical analysis of patient-derived tissue microarrays (TMAs) with publicly available single-cell transcriptomic data, we demonstrate that high stromal PIAS1 expression is associated with improved patient survival and that PIAS1 governs distinct, tumor-suppressive transcriptional programs across key stromal and immune cell types within the OSCC TME. The gene discussed is PIAS1; the disease is neoplasm.