Chemotherapy regimens induce inhibitory immune checkpoint protein expression on stem-like and senescent-like oesophageal adenocarcinoma cells

• DOI: 10.1016/j.tranon.2021.101062
• Publication Date: 2021-03-23T08:45:12Z
• Authors: Maria Davern; Noel E. Donlon; Andrew Sheppard; Fiona O’ Connell; Conall Hayes; Anshul Bhardwaj; Emma Foley; Dermot O’ Toole; Niamh Lynam-Lennon; Narayanasamy Ravi; John V. Reynolds; Stephen G. Maher; Joanne Lysaght
• Keywords: TIGIT; Immune checkpoint

Use of immune checkpoint inhibitors (ICIs) with chemotherapy to enhance responses in oesophageal adenocarcinoma (OAC) is an attractive approach. We identified subpopulations OAC cells expressing inhibitory (IC) ligands (PD-L1, PD-L2 and CD160) receptors (PD-1, TIGIT, TIM-3, LAG-3 A2aR) vitro ex vivo biopsies. Combination regimens FLOT CROSS promote a more immune-resistant phenotype through upregulation IC on vitro. Importantly, this study investigated if cells, enriched for ICs exhibited stem-like senescent-like phentoype. preferentially upregulates PD-L1 cell phenotype, defined by ALDH activity. Expression senescence-associated β-galactosidase induced subpopulation following treatment, along enhanced expression TIM-3 A2aR ICs. Blockade PD-1 signalling apoptosis toxicity Upregulation may represent potential mechanisms chemo-immune resistance. ICIs be required the efficacy immunotherapy patients.