PD-1 and TIGIT blockade differentially affect tumour cell survival under hypoxia and glucose deprived conditions in oesophageal adenocarcinoma; implications for overcoming resistance to PD-1 blockade in hypoxic tumours

Translational Oncology(2022)

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摘要
•PD-1 and TIGIT expression are highly expressed on the surface of oesophageal epithelial cells during the early stages of metaplasia.•Glucose deprivation and hypoxia upregulate PD-1 and TIGIT on the surface of oesophageal adenocarcinoma (OAC) cells in vitro.•PD-1 and TIGIT blockade decrease Bcl-2 and Bcl-xL expression in OAC cells.•PD-1 blockade in OAC cells enhances basal respiration and glycolytic reserve and upregulates GLUT1 on the surface of a subpopulation of OAC cells.•PD-1 inhibition confers a survival advantage to OAC cells under glucose deprivation and hypoxia.•TIGIT blockade decreases OAC cell proliferation and induces OAC cell death under normoxia, hypoxia and nutrient deprivation.•TIGIT blockade increases ECAR yet decreases a range of metabolic parameters in OAC cells.
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关键词
Bcl-xl,GLUT1,Glycolysis,Immune checkpoints,Oxidative phosphorylation
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