title: Upregulation of Immune Checkpoint Molecules, PD-1 and LAG-3, on CD4+ and CD8+ T Cells after Gastric Cancer Surgery.
abstract: BACKGROUND
  Surgery has been reported to suppress cell-mediated immunity; however, the detailed mechanisms responsible for this remain unclear. This study determined the expression of lymphocyte activation gene 3 (LAG-3) and programmed cell death 1 (PD-1) in lymphocytes following surgery for gastric cancer.
  
  
  METHODS
  LAG-3 and PD-1 expression on both CD4+ and CD8+ T cells obtained pre- and post-operatively from gastric cancer patients were evaluated by multicolor flow cytometry.
  
  
  RESULTS
  The total lymphocyte count decreased rapidly from preoperative levels, reaching a minimum on postoperative day 1 and remaining significantly decreased on days 3 and 7. PD-1(+)CD4(+) T cells significantly increased, reaching a maximum on postoperative day 1 and remaining significantly elevated on day 3. PD-1(+)CD8(+) T cells significantly increased and reached a maximum on day 7 before returning to the preoperative level on day 30. There were no statistically significant differences in the frequency of LAG-3(+)CD4(+) or LAG-3(+)CD8(+) T cells after surgery. There were significant positive correlations between PD-1 and LAG-3 expression on both CD4(+) andCD8(+) T cells.
  
  
  CONCLUSIONS
  PD-1 and LAG-3 expression on both CD4(+) and CD8(+) T cells was up-regulated and might be related to impaired cell-mediated immunity after surgery for gastric cancer.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Takaya
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.affiliation: Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Ikeguchi
keywords: T-cell; gastric cancer; lymphocyte activation gene 3; programmed cell death 1