免疫检查点IDO-1、LAG-3、TIM-3与分化型甲状腺癌临床病理特征及预后的相关性

目的:探究3种免疫检查点吲哚胺2, 3-双加氧化酶1(IDO-1)、淋巴细胞活化基因3(LAG-3)、T细胞免疫球蛋白黏蛋白分子3(TIM-3)在分化型甲状腺癌(DTC)中的表达情况以及预后价值。方法:回顾性分析2014年5月至2015年11月于上海交通大学附属第六人民医院行手术治疗的119例DTC患者(男33例，女8...

Correlation of IDO-1, LAG-3 and TIM-3 with clinicopathological features and prognosis of differentiated thyroid cancer

Objective To explore the expression of indoleamine 2,3-dioxygenase 1(IDO-1),lymphocyte-activation gene 3(LAG-3)and T cell immunoglobulin domain and mucin domain-containing molecule 3(TIM-3)in differentiated thyroid cancer(DTC),and the value of them on prognosis.Methods From May 2014 to November 2015,119 DTC patients(33 males,86 females,media age:42 years)who underwent surgical treatment in Shanghai Sixth People′s Hospital were retrospectively analyzed.The expressions of IDO-1,LAG-3 and TIM-3 in the specimens were analyzed by immunohistochemistry and the expression differences between cancer tissues and normal tissues were analyzed byχ² test.The correlation of IDO-1,LAG-3 and TIM-3 with clinical characteristics were analyzed using logistic regression analysis.The patients were followed up for 5 years,and the relationships of the progression-free survival(PFS)rate with the expressions of the three immune checkpoints were analyzed by Kaplan-Meier method,log-rank test and Cox proportional hazard models.Results The overall 5-year PFS rate for 119 DTC patients(median follow-up time:55(2-66)months)was 76.47%(91/119).The positive expression rates of LAG-3 and TIM-3 in cancer tissues were 21.85%(26/119)and 78.15%(93/119)respectively,which were significantly higher than those in normal thyroid tissues(7.34%(8/109)and 62.39%(68/109);χ² values:9.43,6.81,both P<0.05).While the positive expression rate of IDO-1 was 70.59%(84/119)in cancer tissues,which did not show a significant difference from that in normal thyroid tissues(64.22%(70/109);χ²=1.05,P>0.05).Factors associated with the positive expression of LAG-3 included tumors with a single lesion(odds ratio(OR)=0.248,95%CI:0.086-0.716,P=0.010).Log-rank test(χ²=4.96,P=0.026)and multivariate Cox regression analysis(hazard ratio(HR)=2.239,95%CI:1.013-4.592,P=0.046)suggested that LAG-3 positive expression was an independent risk factor of PFS.The same analysis of TIM-3 found no clinicopathological factors related to TIM-3 positive expression(OR:0.309-3.084,all P>0.05)and no association between TIM-3 positive expression and PFS(χ²=0.008,P=0.929).Conclusion The expressions of LAG-3 and TIM-3 are significantly increased in DTC tissues,and the higher expression of LAG-3 is associated with the worse prognosis,suggesting that LAG-3 may be a potential target for immunotherapy in DTC patients.