A Four-Factor Immunoscore System That Predicts Clinical Outcome for Stage II/III Gastric Cancer
A Four-Factor Immunoscore System That Predicts Clinical Outcome for Stage II/III Gastric Cancer
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预测 II/III 期胃癌临床结果的四因素免疫评分系统
DOI：
10.1158/2326-6066.cir-16-0381
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发表时间：
2017-07-01
影响因子：
10.1
通讯作者：
Liu, Yunpeng
中科院分区：
文献类型：
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作者：
Wen, Ti;Wang, Zhenning;Liu, Yunpeng
美国癌症联合委员会(AJCC)的胃癌分期系统不足以预测预后。基于肿瘤或免疫细胞上PD-L1表达、PD-1表达和CD8+T细胞浸润的免疫评分系统更能预测预后，是对AJCC系统的补充。美国癌症联合委员会(AJCC)的分期系统不足以预测可手术的胃癌患者的预后；因此，补充因素正在紧张的研究中。虽然重点放在免疫标记物上，但由于复杂的抗肿瘤免疫反应，单一免疫因素对预后的影响微乎其微。更全面的评估可能会产生更准确的预测。我们通过免疫组织化学染色在两个独立的队列中分析了免疫因素。采用Kaplan-Meier方法分析其与患者生存的关系。我们的免疫核心系统是用COX比例风险分析构建的。PD-L1+免疫细胞(IC)、PD-L1+肿瘤细胞(TC)、PD-1HI和CD8在发现队列中分别为33.33%、31.37%、33.33%和49%，在验证队列中分别为41.74%、17.4%、38.26%和30.43%。PD-L1+ICs和PD-1hi ICs与较差的总生存率(OS)相关，而PD-L1+TCS与较好的OS和临床预后相关，并与更多CD8+T细胞的渗透有关。调整肿瘤/淋巴结/转移(TNM)分期后，这4个因素是独立的预后因素。基于这四个因素的风险比的免疫评分系统进一步将TNM分期相似的胃癌患者分为低、中、高风险组，患者的生存率有显著差异。我们的预后模型预测5年死亡率的受试者操作特征曲线下面积为0.856，优于TNM分期(AuC值为0.676)。因此，这一更全面的免疫评分系统可以提供更准确的预后，是对可手术胃癌患者AJCC分期系统的必要补充。癌症免疫研究；5(7)；524-34。©2017 AACR。
The American Joint Committee on Cancer (AJCC) staging system for gastric cancer is insufficiently prognostic. An immunoscore system based on PD-L1 expression on tumor or immune cells, PD-1 expression, and infiltration of CD8+ T cells was more prognostic and complements the AJCC system. The American Joint Committee on Cancer (AJCC) staging system is insufficiently prognostic for operable gastric cancer patients; therefore, complementary factors are under intense investigation. Although the focus is on immune markers, the prognostic impact of a single immune factor is minimal, due to complex antitumor immune responses. A more comprehensive evaluation may engender more accurate predictions. We analyzed immune factors by immunohistochemical staining in two independent cohorts. The association with patients' survival was analyzed by the Kaplan–Meier method. Our immunoscore system was constructed using Cox proportional hazard analysis. PD-L1+ immune cells (IC), PD-L1+ tumor cells (TC), PD-1hi, and CD8More were found among 33.33%, 31.37%, 33.33%, and 49%, respectively, of patients from the discovery cohort, and 41.74%, 17.4%, 38.26%, and 30.43% from the validation cohort. PD-L1+ ICs and PD-1hi ICs correlated with poorer overall survival (OS), but PD-L1+ TCs correlated with better OS and clinical outcomes and infiltration of more CD8+ T cells. These four factors were independently prognostic after tumor/lymph nodes/metastasis (TNM) stage adjustment. An immunoscore system based on hazard ratios of the four factors further separated gastric cancer patients with similar TNM staging into low-, medium-, or high-risk groups, with significantly different survival. Our prognostic model yielded an area under the receiver operating characteristic curve (AUC) of 0.856 for prediction of mortality at 5 years, superior to that of TNM staging (AUC of 0.676). Thus, this more comprehensive immunoscore system can provide more accurate prognoses and is an essential complement to the AJCC staging system for operable gastric cancer patients. Cancer Immunol Res; 5(7); 524–34. ©2017 AACR.