PBRM1 and neoplasm: This paradox can be resolved by TME heterogeneity: (1) HERV-E overexpression driven by PBRM1 loss promotes immune escape via upregulation of T-cell exhaustion markers (TIM-3, LAG-3) [105, 116]; (2) In inflamed TMEs, PBRM1 deficiency induces cytosolic DNA sensing through defective G2/M checkpoint control, enhancing response to immune checkpoint inhibitors (ICIs) [117]; (3) Hypoxia level and immune cell density determine whether HERVs exert pro-tumor or immunogenic effects [118].