Upregulation of TIM-3 and PD-1 on CD4+ and CD8+ T Cells Associated with Dysfunction of Cell-Mediated Immunity after Colorectal Cancer Operation
Upregulation of TIM-3 and PD-1 on CD4+ and CD8+ T Cells Associated with Dysfunction of Cell-Mediated Immunity after Colorectal Cancer Operation
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发表时间：
2012-03
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通讯作者：
Yosuke Arai;H. Saito;M. Ikeguchi
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作者：
Yosuke Arai;H. Saito;M. Ikeguchi
据报道，手术可以抑制细胞介导的免疫；然而，造成这种情况的详细机制仍不清楚。我们获得了结直肠癌患者术后 CD4+ 和 CD8+ T 细胞上 T 细胞免疫球蛋白结构域和粘蛋白结构域 3 (TIM-3) 以及程序性细胞死亡 1 (PD-1) 表达的信息，并通过多色流式细胞术进行评估。通过酶联免疫吸附测定定量干扰素-γ (IFN-γ) 浓度来确定基于 TIM-3 和 PD-1 表达的 CD4+ 和 CD8+ T 细胞的功能。研究表明，淋巴细胞总数、CD4+ T 细胞和 CD8+ T 细胞数量迅速显着减少。这些免疫细胞在第1天达到最低值，然后增加，但在第3天和第7天仍然显着减少。结直肠手术后PD-1+CD4+T细胞和TIM-3+CD4+T细胞的频率显着增加。与 PD-1+TIM3-CD4+ T 细胞或 PD-1-TIM-3-CD4+ T 细胞的分泌相比，PD-1+TIM-3+CD4+ T 细胞的 IFN-γ 分泌显着减少。此外，与 PD-1-TIM-3+CD8+ T 细胞或 PD-1-TIM-3-CD8+ T 细胞的分泌相比，PD-1+TIM-3+CD8+ T 细胞的 IFN-γ 分泌显着减少。 PD-1和TIM-3的表达与结直肠癌手术后观察到的细胞介导的免疫受损密切相关。围手术期针对 CD4+ 和 CD8+ T 细胞上的 TIM-3 和 PD-1 的新疗法可能为结直肠癌患者的治疗带来突破。
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-γ (IFN-γ) 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-γ 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-γ 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.