Two preclinical studies identified actionable nodes to amplify cancer immunotherapy. One report showed that loss of the E3 ligase TRIM25 enhances T-cell anti‑tumor activity through modulation of the VISTA checkpoint, and a complementary study demonstrated that direct VISTA blockade potentiates anti‑tumor immune responses in multiple models. Researchers published mechanistic data linking these pathways to T-cell regulation and tumor microenvironment remodeling, suggesting combination or sequential targeting strategies to overcome resistance to PD‑1/PD‑L1 therapies. Translational teams will evaluate drug candidates and biomarkers that predict response to VISTA-targeted agents and explore how TRIM25 status may stratify patients for combination regimens.