Increased coexpression of PD-L1 and TIM3/TIGIT is associated with poor overall survival of patients with esophageal squamous cell carcinoma.
Increased coexpression of PD-L1 and TIM3/TIGIT is associated with poor overall survival of patients with esophageal squamous cell carcinoma.
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PD-L1和TIM 3/TIGIT的共表达增加与食管鳞状细胞癌患者的总体生存率低相关
DOI：
10.1136/jitc-2021-002836
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发表时间：
2021-10
影响因子：
10.9
通讯作者：
Ding Z
中科院分区：
文献类型：
--
作者：
Wang P;Chen Y;Long Q;Li Q;Tian J;Liu T;Wu Y;Ding Z
免疫检查点(IC)阻断(ICBS)显著改善实体瘤患者的临床预后。由于单剂免疫球蛋白的客观应答率有限，探索免疫球蛋白与免疫球蛋白的联合应用具有重要意义。应用肿瘤基因组图谱(TCGA)数据库中95例新诊断的食管鳞癌(ESCC)患者的RNA测序数据，探讨ICS的预后意义。应用免疫组织化学方法对58例食管癌组织标本进行了验证。TCGA和VALIDATION结果均提示，程序性细胞死亡1配体1(PD-L1)、T细胞免疫球蛋白和粘蛋白结构域3(TIM3)以及T细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域(TIGIT)的高表达与ESCC患者的总体生存率(OS)低相关。重要的是，PD-L1/TIM3或PD-L1/TIGIT是预测ESCC患者OS差和限制平均生存时间短的最佳组合，是一个独立的预后因素。此外，PD-L1、TIM3和TIGIT与原发灶、区域淋巴结、远处转移分期一起构建的诺模图模型可以简明、准确地预测1年和2年的OS率和中位生存期。PD-L1/TIM3或PD-L1/TIGIT与CD8+T细胞呈正相关。值得注意的是，在ESCC患者中，PD-1和TIM3/TIGIT主要在CD8+肿瘤浸润性淋巴细胞上共表达。ICs的高表达与食管鳞癌患者的OS不良有关。PD-L1/TIM3和PD-L1/TIGIT是预测OS的最佳组合，可能成为未来ICBS治疗ESCC的潜在靶点。
Immune checkpoint (IC) blockades (ICBs) significantly improve patients’ clinical outcomes with solid tumors. Because the objective response rate of single-agent ICB is limited, it is meaningful to explore the combination of ICs for immunotherapy. RNA sequencing data of 95 newly diagnosed patients with esophageal squamous cell carcinoma (ESCC) from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic significance of ICs. The results were validated by immunohistochemistry of 58 ESCC tissue samples from our clinical center. The results of both TCGA and validation data suggested that high expression of programmed cell death 1 ligand 1 (PD-L1), T-cell immunoglobulin and mucin-domain-containing-3 (TIM3), and T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was associated with poor overall survival (OS) of patients with ESCC. Importantly, PD-L1/TIM3 or PD-L1/TIGIT was the optimal combination for predicting poor OS and short restricted mean survival time of patients with ESCC and was an independent prognostic factor. Moreover, a nomogram model constructed by PD-L1, TIM3, and TIGIT together with the primary tumor, regional lymph node, distant metastasis stage could provide a concise and precise prediction of 1-year and 2-year OS rates and median survival time. PD-L1/TIM3 or PD-L1/TIGIT had a positive correlation with CD8+ T cells. Notably, PD-1 and TIM3/TIGIT were primarily coexpressed on CD8+ tumor-infiltrating lymphocyte in patients with ESCC by multiplexed immunofluorescence. High expression of ICs was associated with poor OS of patients with ESCC. PD-L1/TIM3 and PD-L1/TIGIT were the optimal combinations for predicting OS, which might be potential targets for future ICBs therapy of ESCC.
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影响因子：
50.3
作者：
Johnston, Robert J.;Comps-Agrar, Laetitia;Grogan, Jane L.
通讯作者：
Grogan, Jane L.
DOI：
10.1093/jnci/djy088
发表时间：
2018-08-01
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Sauerbrei W;Taube SE;McShane LM;Cavenagh MM;Altman DG
通讯作者：
Altman DG
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
4
作者：
He Y;Cao J;Zhao C;Li X;Zhou C;Hirsch FR
通讯作者：
Hirsch FR
机制驱动的生物标志物指导癌症治疗中的免疫检查点阻断。
DOI：
10.1038/nrc.2016.36
发表时间：
2016-05
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Topalian SL;Taube JM;Anders RA;Pardoll DM
通讯作者：
Pardoll DM