Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma.
Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma.
复制标题
肿瘤浸润免疫细胞在口腔鳞状细胞癌中的预后意义
DOI：
10.1186/s12885-017-3317-2
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发表时间：
2017-05-26
期刊：
影响因子：
3.8
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Fang J;Li X;Ma D;Liu X;Chen Y;Wang Y;Lui VWY;Xia J;Cheng B;Wang Z
背景预后因素有助于癌症的分层和治疗。本研究评估肿瘤浸润性免疫细胞在口腔鳞状细胞癌患者的预后重要性。MethodsProfile浸润性免疫细胞和临床病理数据可为78例口腔鳞癌患者的中位随访时间为48个月。免疫组化检测CD 8、CD 4、T-bet、CD 68、CD 57阳性细胞的浸润强度。采用卡方检验比较免疫标志物表达与临床病理参数的关系。单变量和多变量考克斯比例风险模型用于评估免疫细胞的预后预测能力。结果CD 8、CD 4、T-bet、CD 68和CD 57的平均表达值分别为28.99、62.06、8.97、21.25和15.75个细胞/高倍视野。通过平均值将患者队列分为低表达组和高表达组。高CD 8表达与无区域淋巴结转移相关（p= 0.033）。间质CD 57+细胞丰富的患者显示没有转移到区域淋巴结（p= 0.005）和早期临床分期（p= 0.016）。单因素考克斯回归分析显示，无淋巴结转移（p< 0.001）、临床分期早（TNM分期I/II vs III/IV，p= 0.007）、CD 8和CD 57高表达（p< 0.001）均与总生存期延长呈正相关。多因素考克斯回归分析显示，无淋巴结转移（p= 0.008）、CD 8（p= 0.03）和CD 57（p< 0.001）高表达可能是生存期较好的独立预后指标。在单因素和多因素分析中，CD 4、T-bet和CD 68均与生存无关。ROC曲线和AUC曲线显示，CD 8和CD 57的预测准确性均优于TNM分期的上级。CD 57（AUC = 0.868; 95%CI，0.785-0.950）和CD 8（AUC = 0.784; 95%CI，0.680-0.889）均具有较高的预测准确性，其中CD 57是最佳的预测因子。我们的研究结果表明，口腔鳞癌中存在一个活跃的免疫微环境，可能是免疫药物的靶点。
BackgroundPrognostic factors aid in the stratification and treatment of cancer. This study evaluated prognostic importance of tumor infiltrating immune cell in patients with oral squamous cell carcinoma.MethodsProfiles of infiltrating immune cells and clinicopathological data were available for 78 OSCC patients with a median follow-up of 48 months. The infiltrating intensity of CD8, CD4, T-bet, CD68 and CD57 positive cells were assessed by immunohistochemistry. Chi-square test was used to compare immune markers expression and clinicopathological parameters. Univariate and multivariate COX proportional hazard models were used to assess the prognostic discriminator power of immune cells. The predictive potential of immune cells for survival of OSCC patients was determined using ROC and AUC.ResultsThe mean value of CD8, CD4, T-bet, CD68 and CD57 expression were 28.99, 62.06, 8.97, 21.25 and 15.75 cells per high-power field respectively. The patient cohort was separated into low and high expression groups by the mean value. Higher CD8 expression was associated with no regional lymph node metastasis (p= 0.033). Patients with more abundant stroma CD57+cells showed no metastasis into regional lymph node (p= 0.005), and early clinical stage (p= 0.016). The univariate COX regression analyses showed that no lymph node involvement (p< 0.001), early clinical stage (TNM staging I/II vs III/IV,p= 0.007), higher CD8 and CD57 expression (p< 0.001) were all positively correlated with longer overall survival. Multivariate COX regression analysis showed that no lymph node involvement (p= 0.008), higher CD8 (p= 0.03) and CD57 (p< 0.001) expression could be independent prognostic indicators of better survival. None of CD4, T-bet or CD68 was associated with survival in ether univariate or multivariate analysis. ROC and AUC showed that the predictive accuracy of CD8 and CD57 were all superior compared with TNM staging. CD57 (AUC = 0.868; 95% CI, 0.785–0.950) and CD8 (AUC = 0.784; 95% CI, 0.680–0.889) both provided high predictive accuracy, of which, CD57 was the best predictor.ConclusionTumor stroma CD57 and CD8 expression was associated with lymphnode status and independently predicts survival of OSCC patients. Our results suggest an active immune microenvironment in OSCC that may be targetable by immune drugs.