Stimulator of interferon genes (STING) in renal tumors: Biological bases, diagnostic relevance, and predictive potential.

Renal tumors encompass a diverse group of neoplasms with distinct, morphological, and molecular features. Recent research has highlighted the stimulator of interferon genes (STING) pathway as a key player in tumorigenesis, immune modulation, and autophagy across various renal tumor histotypes. This review explores the biological, diagnostic, prognostic, and therapeutic implications of STING in both epithelial and mesenchymal renal neoplasms. In clear cell renal cell carcinoma, STING expression correlates with aggressive histological features and poor clinical outcomes, suggesting a role in immune evasion and tumor progression. Similarly, in fumarate hydratase-deficient renal cell carcinoma, STING activation, driven by mitochondrial dysfunction and fumarate accumulation, aligns with PD-L1 expression and tumoral inflammatory infiltrate, supporting its potential function as a predictive biomarker of immunotherapy response. In renal perivascular epithelioid cell (PEC) proliferations, widespread STING expression is linked to autophagy regulation and mTOR pathway interaction, offering novel therapeutic insights. The dual role of STING in promoting or suppressing inflammation underscores the therapeutic potential of both agonists and antagonists of this pathway, depending on the specific tumor entity. Moreover, STING's interplay with interferons and cytokines, such as IL-6 and IFNγ, further supports its relevance in modulating immune responses and treatment efficacy. Despite current limitations, accumulating evidence places STING as a promising biomarker and therapeutic target in numerous renal tumors. Future studies are warranted to clarify its mechanistic roles and optimize its clinical application across renal tumor subtypes.