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• W2981896813 abstract "The PD-1/PD-L1 pathway contributes to the metabolic reprogramming of immune cells and tumor cells. However, the mechanism by which PD-L1 regulates glycolysis in human cancer and the relationship between PD-L1 expression, glycose metabolism and anti-tumor immune response remain unclear. We addressed these issues in human non-small-cell lung cancer (NSCLC). Changes in glycolysis-related molecules and glycolytic activity were evaluated in PD-L1low and PD-L1high NSCLC cells after transfection or knockdown of PD-L1, respectively. RNA seq and gene set enrichment analyses (GSEA) was also performed. The association between PD-L1 and immune response-related molecules or glycolysis were analyzed in patients with NSCLC and The Cancer Genome Atlas (TCGA). Transfecting PD-L1 in PD-L1low cells enhanced hexokinase-2 (HK2) expression, lactate production, and extracellular acidification rates, but minimally altered GLUT1 and PKM2 expression and oxygen consumption rates. Consistently, GSEA revealed that the glycolytic pathway was enhanced in PD-L1low cells after PD-L1 transfection. By contrast, knocking-down PD-L1 in PD-L1high cells decreased HK2 expression and glycolysis by suppressing PI3K/Akt and Erk pathways. Immunohistochemistry revealed that PD-L1 expression was positively correlated with HK2 expression in NSCLC tissues from patients (p<0.001). In TCGA analyses, HK2 exhibited a positive linear association with CD274 (PD-L1) expression (p<0.001) but an inverse correlation with the expression of CD4, CD8A, and T-cell effector function-related genes in the CD274high rather than CD274low group. Consistent with this, there were fewer CD8+ T-cells in PD-L1positive/HK2high tumors compared to PD-L1positive/HK2low tumors in squamous cell carcinoma. PD-L1 enhances glycolysis in NSCLC by upregulating HK2, which might dampen anti-tumor immunity. PD-L1 may contribute to NSCLC oncogenesis by inducing metabolic reprogramming and immune checkpoint pathway." @default.
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• W2981896813 date "2019-10-01" @default.
• W2981896813 modified "2023-10-18" @default.
• W2981896813 title "P2.04-42 PD-L1-Mediated Enhancement of Hexokinase 2 Expression Is Inversely Related to T-Cell Effector Gene Expression in Non-Small-Cell Lung Cancer" @default.
• W2981896813 doi "https://doi.org/10.1016/j.jtho.2019.08.1547" @default.
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