Upregulation of TIM-3 and PD-1 on CD4+and CD8+T Cells Associated with Dysfunction of Cell-Mediated Immunity after Colorectal Cancer Operation

作者：Arai Yosuke^*; Saito Hiroaki; Ikeguchi Masahide

来源：Yonago Acta Medica, 2012, 55(1): 1-9.

• colorectal cancer
• programmed cell death 1
• surgical trauma
• T-cell immunoglobulin domain and mucin domain 3

Surgery has been reported to suppress cell-mediated immunity; however, the detailed mechanisms responsible for this remain unclear. We obtained information on expressions of T-cell immunoglobulin domain and mucin domain 3 (TIM-3) and programmed cell death 1 (PD-1) on both CD4+ and CD8+ T cells postoperatively from colorectal cancer patients and evaluated by multicolor flow cytometry. The functions of CD4+ and CD8+ T cells based on TIM-3 and PD-1 expressions were determined by quantitating the concentration of interferon-gamma (IFN-gamma) by enzyme-linked immunosorbent assay. The study demonstrated a rapid and significant decrease in number of total lymphocytes, CD4+ T cells and CD8+ T cells. These immune cells reached the minimum on day 1 and then increased, but still significantly decreased on days 3 and 7. The frequency of PD-1+ CD4+ T cells and TIM-3+ CD4+ T cells significantly increased after colorectal surgery. IFN-gamma secretion by PD-1+ TIM-3+ CD4+ T cells was significantly decreased compared to secretion by either PD-1+ TIM3-CD4+ T cells or PD-1-TIM-3-CD4+ T cells. Furthermore, IFN-gamma secretion by PD-1+ TIM-3+ CD8+ T cells was significantly decreased compared to secretion by either PD-1-TIM-3+ CD8+ T cells or PD-1-TIM-3-CD8+ T cells. The expression of PD-1 and TIM-3 was closely related to impaired cell-mediated immunity that was observed after surgery for colorectal cancer. New treatment targeting TIM-3 and PD-1 on CD4+ and CD8+ T cells during the perioperative period may provide a breakthrough in the treatment of colorectal cancer patients.

• 出版日期2012-3