HIF1A and cancer: This stabilizes the intracellular pH of cancer cells while acidifying the extracellular environment.30,133 HIF-1α induces high expression of tumor-associated carbonic anhydrase (CA), such as CA9 and CA12, which catalyze the reversible hydration of CO2 to carbonic acid.240 In hypoxic environments, the pH of the extracellular environment of cancer cells can be as low as 5.8–6.5,208 which inhibits CTL activation, proliferation, and cytokine production, and also triggers T cell apoptosis.241