Researchers identified RNF128 as a driver of immune resistance in bladder cancer, linking high RNF128 expression to reduced CD8 T-cell infiltration and a less inflamed tumor microenvironment. In functional experiments, RNF128 knockdown and overexpression altered T-cell recruitment and cytotoxic activity, and the gene’s expression correlated with lower T-cell-inflamed signatures in bulk and single-cell analyses. In parallel preclinical work, inhibiting the aryl hydrocarbon receptor (AhR) rewired myeloid–T cell crosstalk and boosted anti-PD-1 responses in mouse and humanized tumor models. The combination of a tumor-intrinsic resistance regulator and an immune-environment lever adds practical targets for next-step translational evaluation.