4.6 Article

Expression of programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand (PD-L1) in adenocarcinomas of the gastroesophageal junction change significantly after neoadjuvant treatment

Journal

EJSO
Volume 48, Issue 2, Pages 383-390

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.ejso.2021.08.016

Keywords

Adenocarcinoma of the gastroesophageal junction; Neoadjuvant chemotherapy; Immunotherapy; Programmed cell death (PD-1); Programmed cell death ligand (PD-L1)

Funding

  1. Promedica Stiftung [1406/M, 1412/M]
  2. Swiss Cancer Research Foundation [KFS-4243-08-2017]
  3. Swiss National Science Foundation [PMPDP3_151326]
  4. Clinical Research Priority Program (CRPP) of the University of Zurich
  5. European Academy of Dermatology and Venereology [PPRC-2019-20]
  6. BMS
  7. Roche

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This study investigated the impact of neoadjuvant chemotherapy on the expression of PD-1 and PD-L1 in adenocarcinomas of the gastroesophageal junction. The results showed a significant increase in PD-1 expression and a decrease in PD-L1 expression after neoadjuvant therapy. These findings suggest that the combined use of cytotoxic chemotherapy and PD-1 axis blockade may be beneficial for patients with adenocarcinomas of the gastroesophageal junction.
Background: The effects of cytotoxic chemotherapy on the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in cancer cells and peritumoral cells are unclear. The aim of this study was to investigate the impact of neoadjuvant chemotherapy on PD-1 and PD-L1 expression in adenocarcinomas of the gastroesophageal junction. Methods: PD-1 and PD-L1 expression in cancer cells and tumor-infiltrating lymphocytes in paired diagnostic biopsies and surgical specimens from patients with pretreated and curatively resected adenocarcinomas of the gastroesophageal junction were evaluated by immunohistochemistry. Results: Paired tumor samples were available from 40 patients. PD-1 expression in cancer cells (p < 0.001; Exact Symmetry Test) and tumor-infiltrating lymphocytes (p < 0.001; Exact Symmetry Test) increased significantly after neoadjuvant therapy. Furthermore, we observed a significant decrease in PD-L1 expression in cancer cells (p = 0.003) after neoadjuvant therapy was observed. Conclusion: In this study we could show that tumor-cell expression of PD-1 and PD-L1 was significantly altered in patients with adenocarcinomas of the gastroesophageal junction after receiving neoadjuvant chemotherapy. Based on these observations, patients might profit from the combined use of cytotoxic chemotherapy and the blockade of the PD-1 axis. (C) 2021 Published by Elsevier Ltd.

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