CA9 and neoplasm: Moreover, key regulators of hypoxia showed the same trend in the EGFRHIGH/METHIGH subcluster and the treatment groups (HIF1A, HDAC1, KDM1A, KDM2A, CA9, VEGFA, and TWIST1; Fig. 5D), suggesting that the tumor in the HNSCC PDX mice treated with pembrolizumab feasibly had an acidic environment by favoring anaerobic metabolism of glucose in the TME.