CA9 and neoplasm: Lactate transported out of tumor cells lowers the extracellular pH from approximately 7.4 on the leading edges to approximately 6.0 in the central necrotic zones of the tumor.71,72 Cells re-establish intracellular pH levels by importing additional bicarbonate ions, facilitated by the hypoxia-induced downstream protein carbonic anhydrase IX (CA-IX).73 Acidification of the tumor prompts significantly higher levels of immunosuppression and GSC migration and proliferation.74–76