HIF1A and neoplasm: However, tumor cells develop adaptive mechanisms to neutralize the intracellular pH via proton transporters, allowing them to survive and thrive in an acidic TME.16,17 Tumor acidity is associated with disease progression, immune evasion, and therapeutic resistance through multiple interconnected mechanisms.18–22 It stabilizes and activates HIF-1α, leading to the upregulation of angiogenic factors, and enhancing glycolytic metabolism, thereby maintaining a hostile and immunosuppressive TME.