In parallel, extracellular acidification stimulates CAFs, promoting angiogenesis, ECM remodeling, and immunosuppression (Supplementary Fig. 7h, i).49–53 These findings highlight a broader oncogenic role for CA9 beyond pH regulation, suggesting that a deeper investigation into the extrinsic effects of CA9 could provide novel insights into CRC malignancy in acidic TMEs. The gene discussed is CA9; the disease is colorectal carcinoma.