Hyakudomi Miki, Matsubara Takeshi, Hyakudomi Ryoji, Yamamoto Tetsu, Kinugasa Shoichi, Yamanoi Akira, Maruyama Riruke, Tanaka Tsuneo
Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Enyacho 89/1, Izumo, Japan.
Ann Surg Oncol. 2008 Jun;15(6):1775-82. doi: 10.1245/s10434-008-9876-3. Epub 2008 Mar 25.
Fractalkine (CX3CL1) is the only CX3C chemokine that can chemoattract natural killer (NK) cells, CD8+ T cells, monocytes, and dendritic cells. Although experimental studies have demonstrated that Fractalkine expression by tumor cells is related to the infiltrating lymphocytes and initiates antitumor immunity, the clinical significance of Fractalkine remains to be elucidated in gastric adenocarcinoma.
Tissue sections from 158 patients with curatively resected T2 or T3 gastric adenocarcinoma were immunohistochemically stained for Fractalkine. Furthermore, to evaluate CD8+ T cells and NK cells infiltration, antibodies to CD8 and CD57 protein were respectively used for immunohistochemistry.
A significant direct correlation was observed between the Fractalkine scores and the number of CD8+ T cells and NK cells using the Spearman rank correlation coefficient test (P = .0080, .0031, respectively). Furthermore, the high Fractalkine expression group (n = 67) showed a significantly better prognosis than the low Fractalkine expression group (n = 91) regarding the disease-free survival (P = .0016). In a multivariate analysis, the Fractalkine expression was identified as one of the independent prognosticators for disease-free survival (risk ratio, 2.5; P = .0147).
These data suggest that the expression of Fractalkine by tumor cells enhances the recruitment of CD8+ T cells and NK cells and induces both innate and adaptive immunity, thereby yielding a better prognosis in gastric adenocarcinoma. Fractalkine is a new independent predictor of the prognosis and can be a novel candidate for development of a more effective therapeutic strategy for gastric adenocarcinomas.
趋化因子(CX3CL1)是唯一能趋化自然杀伤(NK)细胞、CD8 + T细胞、单核细胞和树突状细胞的CX3C趋化因子。尽管实验研究表明肿瘤细胞表达的趋化因子与浸润淋巴细胞有关并启动抗肿瘤免疫,但趋化因子在胃腺癌中的临床意义仍有待阐明。
对158例接受根治性切除的T2或T3期胃腺癌患者的组织切片进行趋化因子免疫组织化学染色。此外,为评估CD8 + T细胞和NK细胞浸润情况,分别使用抗CD8和CD57蛋白的抗体进行免疫组织化学检测。
使用Spearman等级相关系数检验发现,趋化因子评分与CD8 + T细胞和NK细胞数量之间存在显著的直接相关性(P值分别为0.0080和0.0031)。此外,就无病生存期而言,趋化因子高表达组(n = 67)的预后明显优于趋化因子低表达组(n = 91)(P = 0.0016)。在多变量分析中,趋化因子表达被确定为无病生存期的独立预后因素之一(风险比,2.5;P = 0.0147)。
这些数据表明,肿瘤细胞表达的趋化因子可增强CD8 + T细胞和NK细胞的募集,并诱导先天免疫和适应性免疫,从而使胃腺癌患者预后更好。趋化因子是一种新的独立预后指标,可能成为开发更有效胃腺癌治疗策略的新候选指标。