776 A role for immune checkpoint blockade to enhance T cell-mediated responses in combination with chemotherapy in oesophageal adenocarcinoma

BackgroundCombining immune checkpoint inhibitors (ICIs) with immunogenic chemotherapies is a promising approach in oesophageal adenocarcinoma (OAC) to convert ‘cold’ tumours to ‘hot’ tumours expanding the efficacy of ICIs to a greater spectrum of patients.1 However, there is a vast array of immune checkpoints (ICs) expressed by T cells and the effect of ICIs in combination with chemotherapy regimens is largely unknown.2 MethodsThe expression profile of a range of ICs on circulating and tumour-infiltrating T cells was assessed using flow cytometry prior to and post-neoadjuvant treatment and correlated with clinical parameters (n=20). PBMCs isolated from OAC blood were treated with single agent ICIs alone (single agent anti-PD-1, anti-PD-L1, anti-A2aR and anti-TIM-3 inhibition) and in combination with FLOT (5-Fluorouracil, oxaliplatin and docetaxel) and CROSS (carboplatin and paclitaxel) chemotherapy regimens. The production of anti-tumour cytokines by T cells was assessed in vitro by flow cytometry (n=6).ResultsIn the treatment-naïve and post-treatment setting, a range of ICs were expressed by circulating T cells and were significantly increased on tumour-infiltrating T cells, which included PD-L1, PD-L2, CD160, PD-1, CTLA-4, TIGIT, TIM-3, LAG-3, A2aR and ICOS (p