Akagi Junji, Baba Hideo
Department of Surgery, Tamana Regional Health Medical Center, Tamana, Kumamoto 865-0005, Japan.
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Oncol Lett. 2018 Jun;15(6):9257-9263. doi: 10.3892/ol.2018.8451. Epub 2018 Apr 10.
Cluster of differentiation (CD)8+CD57+ T cells are derived through the CD8+ T cell-differentiation signaling pathway from early differentiated CD27+CD8+CD57-T cells (early-CD8+ T cells) to terminal-differentiated CD27-CD8+CD57+ T cells (terminal-CD8+ T cells) via intermediate-differentiated CD27+CD8+CD57+ T cells (intermediate-CD8+ T cells). The increase of CD8+CD57+ T cells in the peripheral blood of patients with cancer has been associated with prognosis, which suggests their suitability as a candidate immunological marker. The present study investigated the association of these CD57-related CD8+ T cell populations in the peripheral blood of 100 Stage IV cancer patients with progression-free survival (PFS), using a Cox regression model. Univariate analysis indicated that early- and intermediate-CD8+ T cells were associated with shorter PFS, whereas terminal-CD8+ T cells were associated with longer PFS. A strong inverse correlation was observed between early- and terminal-CD8+ T cells, and multivariate analysis demonstrated that the CD57 ratio (terminal-CD8+ T cells/early-CD8+ T cells) was a more significant independent prognostic factor compared with early- or terminal-CD8+ T cells. Patients with a higher CD57 ratio had a significantly longer PFS compared with those with a lower CD57 ratio, in whom terminal-CD8+ T cells were supposed to be predominant. Conversely, results indicated inhibition of the CD8+ T cell differentiation signaling pathway in patients with a low CD57 ratio, which lead to a predominance of early-CD8+ T cells, a characteristic of immunosuppressive cells. The present findings suggested that the CD57 ratio appears to be a powerful immunological prognostic parameter obtained from the peripheral blood, precisely reflecting the state of CD8+ T cell-differentiation.
分化簇（CD）8⁺CD57⁺ T细胞通过CD8⁺ T细胞分化信号通路，从早期分化的CD27⁺CD8⁺CD57⁻ T细胞（早期CD8⁺ T细胞）经中间分化的CD27⁺CD8⁺CD57⁺ T细胞（中间CD8⁺ T细胞）分化为终末分化的CD27⁻CD8⁺CD57⁺ T细胞（终末CD8⁺ T细胞）。癌症患者外周血中CD8⁺CD57⁺ T细胞的增加与预后相关，这表明它们适合作为候选免疫标志物。本研究使用Cox回归模型，调查了100例IV期癌症患者外周血中这些与CD57相关的CD8⁺ T细胞群体与无进展生存期（PFS）的关系。单因素分析表明，早期和中间CD8⁺ T细胞与较短的PFS相关，而终末CD8⁺ T细胞与较长的PFS相关。早期和终末CD8⁺ T细胞之间观察到强烈的负相关，多因素分析表明，与早期或终末CD8⁺ T细胞相比，CD57比值（终末CD8⁺ T细胞/早期CD8⁺ T细胞）是更显著的独立预后因素。与CD57比值较低（终末CD8⁺ T细胞占优势）的患者相比，CD57比值较高的患者PFS显著更长。相反，结果表明CD57比值低的患者中CD8⁺ T细胞分化信号通路受到抑制，导致早期CD8⁺ T细胞占优势，这是免疫抑制细胞的一个特征。本研究结果表明，CD57比值似乎是一个从外周血获得的强大免疫预后参数，准确反映了CD8⁺ T细胞分化状态。
