780P - Effect of neoadjuvant chemotherapy on the programmed death-1 pathway in esophageal and gastric cancer

Abstract

BackgroundEsophageal and gastric (EG) cancers stand for a considerable amount of cancer cases and deaths worldwide. Although addition of neoadjuvant and/or adjuvant therapy has led to an improved survival in patients with resectable tumours, there is still a great unmet need for novel treatment strategies and complementary biomarkers. This study examined the effect of neoadjuvant chemotherapy on the expression of programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) in EG adenocarcinoma, as well as the associations of PD-1 and PD-L1 expression with histopathological response and clinical outcome. MethodsImmunohistochemical expression of PD-1 on tumour-infiltrating immune cells (TIC) and of PD-L1 on tumour cells (TC) and TIC was assessed on paired pre-treatment biopsies, post-treatment resected primary tumours and a subset of paired lymph node metastases from a consecutive cohort of 148 patients with neoadjuvant +/- adjuvant treated EG adenocarcinoma. ResultsPD-1 expression was significantly higher in resected tumours and in lymph node metastases compared to biopsies, but the expression of PD-L1TC and PD-L1 TIC was similar before and after neoadjuvant therapy. PD-1 expression was not associated with histopathological response or with survival. Positive PD-L1TC expression in biopsies was significantly associated with histopathological response but not with survival, whereas positive PD-L1TC expression in resected tumours signified a reduced overall survival. High PD-L1 TIC expression in biopsies, but not in resected tumours, was significantly associated with a prolonged overall survival. ConclusionsExpression of PD-1, but not of PD-L1, is augmented after neoadjuvant treatment. Chemotherapy may however evoke more resistant subsets of PD-L1 positive TC, thus indicating a need for alternative treatment strategies in the adjuvant setting. Legal entity responsible for the studyLund University. FundingSUS Stiftelse och Donationer Fru Berta Kamprads Stiftelse Vetenskapliga rådet, Projektmedel för forsknings- och Utvecklingsarbete. DisclosureAll authors have declared no conflicts of interest.