Department of Hematology-Oncology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Tayouan, Taiwan.
Int J Cancer. 2013 Mar 15;132(6):1341-50. doi: 10.1002/ijc.27784. Epub 2012 Sep 18.
Activated T regulatory (T(reg)) cells are potent suppressors that mediate immune tolerance. We investigated the relationship between activated T(reg) cells and the progression of human colon cancer. We designed a cross-sectional study of CD4(+) Foxp3(+) T cells from peripheral blood, primary tumor and nontumor colon tissue of 42 patients with colon cancer and correlated the percentages of different subgroups of T(reg) cells with colon cancer stage. The phenotypes, cytokine-release patterns and suppression ability of these T(reg) cells were analyzed. We found that T(reg) cells increased significantly in both peripheral blood and cancer tissue. In addition, the T(reg) cells expressed significantly lower levels of CCR7, CD62L and CD45RA in comparison to normal volunteers. Further dividing T(reg) cells into subgroups based on Foxp3 and CD45RA expression revealed that both activated T(reg) cells (Foxp3(hi) CD45RA(-)) and nonsuppressive T(reg) cells (Foxp3(lo) CD45RA(-)), but not resting T(reg) cells (Foxp3(low) CD45RA(+)), increased in the peripheral blood and cancer tissue of patients with colon cancer. Only the activated T(reg) cells expressed significantly higher levels of tumor necrosis factor receptor 2 and cytotoxic T-cell antigen-4. Activated T(reg) cells, however, secreted significantly lower levels of effector cytokines (interleukin-2, tumor necrosis factor-α and interferon-γ) than did resting T(reg) cells and nonsuppressive cells upon ex vivo stimulation. Activated, but not resting, T(reg) cells in cancer tissue correlated with tumor metastases. In summary, we confirmed that activated T(reg) cells are a distinct subgroup with effector memory phenotype and fully functional regulatory activity against human colorectal cancer immunity.
活化的调节性 T 细胞（Treg）是具有免疫抑制功能的强效抑制细胞。我们研究了活化的 Treg 细胞与人类结肠癌进展之间的关系。我们对 42 例结肠癌患者的外周血、原发肿瘤和非肿瘤结肠组织中的 CD4+Foxp3+T 细胞进行了横断面研究，并将不同亚群 Treg 细胞的比例与结肠癌分期相关联。分析了这些 Treg 细胞的表型、细胞因子释放模式和抑制能力。我们发现，外周血和肿瘤组织中 Treg 细胞均显著增加。此外，与正常志愿者相比，Treg 细胞表达的 CCR7、CD62L 和 CD45RA 水平明显降低。进一步根据 Foxp3 和 CD45RA 的表达将 Treg 细胞分为亚群，发现活化的 Treg 细胞（Foxp3(hi) CD45RA(-)）和非抑制性 Treg 细胞（Foxp3(lo) CD45RA(-)），而不是静息 Treg 细胞（Foxp3(low) CD45RA(+)），在结肠癌患者的外周血和肿瘤组织中均增加。只有活化的 Treg 细胞表达明显更高水平的肿瘤坏死因子受体 2 和细胞毒性 T 细胞抗原 4。然而，与静息 Treg 细胞和非抑制性细胞相比，活化的 Treg 细胞在体外刺激时分泌的效应细胞因子（白细胞介素-2、肿瘤坏死因子-α和干扰素-γ）水平明显降低。肿瘤组织中的活化 Treg 细胞，但不是静息 Treg 细胞，与肿瘤转移相关。总之，我们证实了活化的 Treg 细胞是一个具有效应记忆表型和对人类结直肠癌细胞免疫完全调节活性的独特亚群。
