Programmed death ligand 2 expression plays a limited role in adenocarcinomas of the gastroesophageal junction after preoperative chemotherapy

Gerd Jomrich; Dagmar Kollmann; Lavinia Wilfing; Sanja Radosavljevic; Dariga Ramazanova; Robin Ristl; Richard P Grose; Aysegül Ilhan-Mutlu; Matthias Preusser; Christina Fassnacht; Yi-Chien Tsai; Emmanuella Guenova; Sebastian F Schoppmann

doi:10.1007/s10353-021-00700-4

Programmed death ligand 2 expression plays a limited role in adenocarcinomas of the gastroesophageal junction after preoperative chemotherapy

Eur Surg. 2021;53(6):287-293. doi: 10.1007/s10353-021-00700-4. Epub 2021 May 5.

Authors

Affiliations

¹ Department of Surgery, Comprehensive Cancer Center Vienna, Upper-GI-Service, GET-Unit, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
² Section for Medical Statistics (IMS), Center of Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
³ Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, EC1M 6BQ London, UK.
⁴ Division of Oncology, Department of Medicine I and Comprehensive Cancer Center, GET-Unit, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria.
⁵ Department of Dermatology, University Hospital Zurich and Faculty of Medicine, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
⁶ Department of Dermatology, Lausanne University Hospital (CHUV) and Faculty of Biology and Medicine, University of Lausanne, Av de Beaumont 29, 1011 Lausanne, Switzerland.

Abstract

Background: The effects of cytotoxic chemotherapy on the expression of programmed death ligand 2 (PD-L2) are unknown and little is known about how the tumor microenvironment changes following neoadjuvant chemotherapy in locally advanced gastroesophageal adenocarcinomas (AEG). Recently, a number of studies reported that cytotoxic chemotherapy affects the expression levels of programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1). Regarding PD-L2, the second known ligand of PD‑1, no data on potential changes in expression patterns in patients with preoperatively treated AEG are available. The aim of this study was to investigate the impact of cytotoxic chemotherapy on PD-L2 expression in patients with resectable AEG.

Methods: Consecutive patients with locally advanced AEG treated with preoperative cytotoxic chemotherapy were included. PD-L2 expression by cancer cells (CCs) and tumor-infiltrating lymphocytes (TILs) was investigated in samples of paired diagnostic biopsies and resected tumor specimens by immunohistochemistry using two different anti-PD-L2 antibodies.

Results: Included were 40 patients with AEG and available paired tumor tissue samples. PD-L2 expression was observed in one diagnostic biopsy sample by CCs and in one diagnostic biopsy sample by TILs. There was no difference concerning the expression levels measured by the two antibodies.

Conclusion: In contrast to previously published studies reporting PD-L2 expression rates of up to 50% in AEGs, in our cohort, PD-L2 expression seems to play no significant role in AEG.

Keywords: Adenocarcinoma of the gastroesophageal junction; Immunotherapy; Neoadjuvant therapy; PD-L2.