Intratumoral IL-17+ Cells and Neutrophils show Strong Prognostic Significance in Intrahepatic Cholangiocarcinoma
Intratumoral IL-17+ Cells and Neutrophils show Strong Prognostic Significance in Intrahepatic Cholangiocarcinoma
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DOI：
10.1245/s10434-012-2268-8
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发表时间：
2012-08-01
影响因子：
3.7
通讯作者：
Zhou, Jian
中科院分区：
文献类型：
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作者：
Gu, Fang-Ming;Gao, Qiang;Zhou, Jian
肿瘤部位的炎症反应对肿瘤的进展既有不利的影响，也有有益的影响。本研究旨在评估肿瘤浸润性炎症细胞在肝内胆管细胞癌(ICC)患者中的临床意义。应用组织芯片和免疫组织化学方法分析IL-17(+)、FOXP3(+)、CD8(+)、CD66b(+)细胞和微血管密度(CD34)在不同显微解剖区域的分布及其临床意义。IL-17(+)细胞、FOXP3(+)淋巴细胞、CD66b(+)中性粒细胞和微血管主要集中在肿瘤内(IT)区，而CD8(+)淋巴细胞在肿瘤侵袭前沿最为丰富。在单变量分析中，IL-17(IT)(+)和中性粒细胞(IT)的升高与患者的存活率显著相关。多因素分析显示，IL-17(IT)(+)(危险比[HR]=1.5 9；95%可信区间[CI]1.05~2.41；P=0.028)、中性粒细胞(IT)(HR=1.76；95%CI，1.16~2.65；P=0.007)及其组合(HR 2.8；95%CI 1.72~4.57；P<；0.001)是独立的预后因素，优于传统的临床病理特征，如肝内转移和TNM分期。IL-17(IT)(+)与有无淋巴结转移、肝内转移和晚期相关，而中性粒细胞(IT)与血管侵犯相关。此外，IL-17(+)细胞密度、中性粒细胞密度和微血管密度之间也呈显著正相关。我们的数据表明，瘤内IL-17(+)细胞和中性粒细胞是预测ICC患者预后的新的、强有力的指标。
Inflammatory reactions at a tumor site have both detrimental and beneficial effects on tumor progression. This study was designed to assess the clinical significance of tumor-infiltrating inflammatory cells in patients with intrahepatic cholangiocarcinoma (ICC).A total of 123 consecutive ICC patients who underwent curative resection were enrolled. Tissue microarray and immunohistochemistry were used to analyze the distribution and clinical relevance of IL-17(+), FOXP3(+), CD8(+), CD66b(+) cells, and microvessel density (CD34) in different microanatomical areas.IL-17(+) cells, FOXP3(+) lymphocytes, CD66b(+) neutrophils, and microvessels were enriched predominantly in intratumor (IT) area, whereas CD8(+) lymphocytes were most abundant in tumor invasive front. On univariate analyses, increasing IL-17 (IT) (+) and neutrophils(IT) were significantly associated with worse patient survival. Multivariate analyses revealed that IL-17 (IT) (+) (hazard ratio [HR] = 1.59; 95% confidence interval [CI], 1.05-2.41; P = 0.028), neutrophils(IT) (HR = 1.76; 95% CI, 1.16-2.65; P = 0.007), and their combination (HR 2.8; 95% CI 1.72-4.57; P < 0.001) were independent prognostic factors, which were superior to conventional clinicopathologic features, such as intrahepatic metastasis and TNM stage. IL-17 (IT) (+) significantly correlated with the presence of lymph node metastasis, intrahepatic metastasis, and advanced stages, whereas neutrophils(IT) correlated with the presence of vascular invasion. In addition, significant positive correlations were detected among densities of IL-17(+) cells, neutrophils, and microvessel density.Our data suggested that intratumor IL-17(+) cells, neutrophils are novel, powerful predictors of prognosis in patients with ICC.