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LDHA and SLC16A3 are important regulators of glycolytic pathways and were upregulated in EGFRHIGH/METHIGH tumor subcluster of HNSCC PDX (YHIM-3003). A, Correlation between expression of EGFR and biomarkers based on TCGA database. LDHA and SLC16A3 expression was positively correlated with expression of EGFR in both HNSCC and LUSC. B, Expression of LDHA and SLC16A3 was significantly increased in EGFRHIGH/METHIGH tumor subcluster (EMHIGH) of HNSCC PDX (left). Additionally, expression of LDHA and SLC16A3 increased in pembrolizumab treated group. C, Regulators of glycolysis (HK2, GPI, ALDOA, PGK1, PGAM1, ENO1, ENO2) comparatively increased in the EMHIGH tumor subcluster (left) and pembrolizumab treated group (right). D, Regulators of hypoxia (HIF1A, HDAC1, KDM1A, KDM2A) and downstream signaling markers (CA9, VEGFA, TWIST1) increased in the EMHIGH tumor subcluster (left) and pembrolizumab treated group (right). E, Total protein and surface expression of EGFR and MET demonstrated strong correlation in HNSCC and LUSC cell lines (left). H1703, LUSC human cancer cell, was treated with IFNγ for 24 hours to mimic the physiological response of pembrolizumab in the TME (right). Induction of IFNγ, though not significant, upregulated the expression of pEGFR, while pMET level significantly increased (P F, Protein expression of EGFR/p-EGFR, MET/p-MET, MCT4 (SLC16A3), and LDHA after 72 hours of amivantamab at 10 mg/mL in H1703. IFNγ was treated at 100 ng/mL for 24 hours (left). Amivantamab reduced the expression of these genes under IFNγ-induced conditions (right).
Lim et al. (Wed,) studied this question.