Upregulation of Immune Checkpoint Molecules, PD-1 and LAG-3, on CD4+ and CD8+ T Cells after Gastric Cancer Surgery

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. CONCLUSION 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.