Potential therapeutic strategy for gastric cancer peritoneal metastasis by NKG2D ligands-specific T cells

Abstract

Xianqiang Liu,1 Meili Sun,2 Shui Yu,3 Kai Liu,4 Xirui Li,5 Huan Shi6 1Department of Breast and Thyroid Surgery, 2Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, 3Department of Radiation Oncology, 4Department of Gastrointestinal Surgery, 5Medical Department, 6Department of Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, People’s Republic of China Purpose: Despite advancements in its treatment, gastric cancer continues to be one of the leading causes of cancer deaths worldwide. Adoptive transfer of chimeric antigen receptor-modified T cells is a promising antitumor therapy for many cancers. The purpose of this study was to construct a chimeric receptor linking the extracellular domain of NKG2D to the CD28 and CD3zeta chain intracellular domains to target gastric cancers that expressed NKG2D ligands.Methods: Expression of NKG2D ligands including MICA, MICB, and ULBP1–3 in a gastric cancer cell line and primary gastric cancer cells from ascites samples were analyzed using flow cytometry. Co-culture experiments were performed by incubating chNKG2D T cells with gastric cancer cell lines and with primary human gastric cancer cells isolated from ascites and by measuring cytokine and chemokine release and cytotoxicity.Results: Gastric cancer cell lines and ascites-derived primary human gastric cancer cells expressed high levels of MICA, MICB, and ULBP2. ChNKG2D T cells secreted proinflammatory cytokines and chemokines when cultured with these cancer cells. In addition, chNKG2D T cells lysed gastric cancer cell lines and the ascites-derived primary human gastric cancer cells.Conclusion: These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for gastric cancer with peritoneal metastasis. Keywords: chimeric antigen receptor, T cells, immunotherapy