We thus hypothesize that combining PT2385 with ICB takes advantage of targeting non-overlapping pathways to potentiate anti-tumor immunity, with PD-1 and TIM-3 blockade primarily reactivating T cell function, while HIF-2α inhibition mitigates other immunosuppressive mechanisms mediated by hypoxia, TAMs, or Tregs [13, 36, 41]. The gene discussed is EPAS1; the disease is neoplasm.