Effect of neoadjuvant chemotherapy on the Programmed Death-1 pathway in esophageal and gastric cancer

Date 29 September 2019
Event ESMO 2019 Congress
Session Poster Display session 2
Topics Oesophageal Cancer
Gastric Cancer
Presenter Maria Svensson
Citation Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247
Authors M.C. Svensson1, A. Lindén1, J. Nygaard1, C. Hedner1, B. Nodin1, D. Borg1, K. Leandersson2, K. Jirström1
  • 1Department Of Clinical Sciences Lund, Oncology And Pathology, Lund University, Lund, Sweden, Lund University, 221 85 - Lund/SE
  • 2Cancer Immunology, Department Of Translational Medicine, Lund University, Malmö, Sweden, Lund University, 221 85 - Lund/SE

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Lund University.

Funding

SUS Stiftelse och Donationer Fru Berta Kamprads Stiftelse Vetenskapliga rådet, Projektmedel för forsknings- och Utvecklingsarbete.

Disclosure

All authors have declared no conflicts of interest.