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.

ABSTRACT: Recent studies have demontrated that immune checkpoint receptors are expressed on the surface of oesophageal adenocarcinoma (OAC) cells and might confer a survival advantage. This study explores the role of PD-1 and TIGIT signalling in OAC cells in either promoting or inhibiting the survival of OAC cells under characteristic features of the tumour microenvironment including nutrient-deprivation and hypoxia. PD-1 and TIGIT are expressed in normal and pre-malignant oesophageal epithelial cells and this expression significantly decreases along the normal- Barrett's Oesophagus- OAC disease sequence. However, glucose-deprivation and hypoxia significantly upregulated PD-1 and TIGIT on the surface of OAC cells in vitro. PD-1 blockade decreased OAC cell proliferation under normoxia but enhanced pr

SUBMITTER: Davern M 

PROVIDER: S-EPMC8894275 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature