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. Issue 2 (February 2022) - Jomrich, Gerd
Abstract: 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. Highlights: The introduction of immunotherapy represents a paradigm shift in treating cancer. A number of studies described synergism between cytotoxic chemotherapy and PD-1/PD-L1 immunotherapy. Our findings suggest that combining cytotoxic chemotherapy with checkpoint inhibitors represents an beneficial option for AEG patients.