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

Abstract Background Esophageal 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. Methods Immunohistochemical 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. Results PD-1 expression was significantly higher in resected tumours and in lymph node metastases compared to biopsies, but the expression of PD-L1 TC 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-L1 TC expression in biopsies was significantly associated with histopathological response but not with survival, whereas positive PD-L1 TC 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. Conclusions Expression 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 study Lund University. Funding SUS Stiftelse och Donationer Fru Berta Kamprads Stiftelse Vetenskapliga radet, Projektmedel for forsknings- och Utvecklingsarbete. Disclosure All authors have declared no conflicts of interest.