Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients
Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients
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DOI：
10.1007/s10120-016-0631-3
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发表时间：
2017-05-01
期刊：
影响因子：
7.4
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Kawazoe, Akihito;Kuwata, Takeshi;Ochiai, Atsushi
针对程序性死亡1（PD-1）及其配体程序性死亡配体1（PD-L1）的抗体最近在胃癌（GC）中显示出有希望的结果。PD-L1表达、肿瘤浸润淋巴细胞（TIL）的存在和错配修复（MMR）缺陷已被提议作为抗PD-1/PD-L1抗体的预测生物标志物。本研究的目的是探讨胃癌中PD-L1表达与TIL、MMR和EB病毒（EBV）状态的临床相关性。我们对487例接受胃切除术的晚期胃癌患者进行了组织芯片分析。通过免疫组织化学评价肿瘤细胞（TC）和肿瘤浸润免疫细胞（TIIC）上的PD-L1表达、TIL密度和MMR状态。原位杂交检测EB病毒，PD-L1在TC和TIIC上的表达、MMR缺陷和EB病毒阳性分别为22.8%、61.4%、5.1%和5.1%。PD-L1表达在老年人中更常见。（TC P = 0.002），男性（TC P = 0.029; TIIC P = 0.043），在具有实体型组织学特征的低分化腺癌患者中在MMR缺陷患者（TC P <0.001; TIICs P <0.001）和EBV阳性患者（TC P = 0.001; TIICs P = 0.050）中。PD-L1表达与高密度的CD 3阳性、CD 8阳性或叉头盒P3阳性TIL之间存在强相关性（TC P < 0.001; TIIC P < 0.001）。多因素分析显示，PD-L1表达与肿瘤浸润性淋巴细胞（TILs）高密度、MMR缺陷、EBV阳性等临床病理特征相关，但不是独立的预后因素。
Antibodies against programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) have recently demonstrated promising results in gastric cancer (GC). PD-L1 expression, the presence of tumor-infiltrating lymphocytes (TILs), and mismatch repair (MMR) deficiency have been proposed as predictive biomarkers for anti-PD-1/PD-L1 antibodies. The aim of this study was to investigate the clinical relevance of PD-L1 expression with TIL, MMR, and Epstein-Barr virus (EBV) status in GC.We performed a tissue microarray analysis in 487 advanced GC patients who underwent gastrectomy. PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (TIICs), the densities of TILs, and MMR status were evaluated by immunohistochemistry. EBV was detected by in situ hybridization.PD-L1 expression on TCs and TIICs, MMR deficiency, and EBV positivity were identified in 22.8, 61.4, 5.1, and 5.1 % cases respectively. PD-L1 expression was more frequently observed in the elderly (TCs P = 0.002), in males (TCs P = 0.029; TIICs P = 0.043), in patients with poorly differentiated adenocarcinoma with solid-type histological features (TCs P < 0.001; TIICs P < 0.001), in patients with MMR deficiency (TCs P < 0.001; TIICs P < 0.001), and in patients with EBV positivity (TCs P = 0.001; TIICs P = 0.050). Strong association was observed between PD-L1 expression and high densities of CD3-positive, CD8-positive, or forkhead box P3 positive TILs (TCs P < 0.001; TIICs P < 0.001). Neither PD-L1 expression on TCs nor that on TIICs was an independent prognostic factor in multivariate analysis.In GC, PD-L1 expression was associated with distinct clinicopathological features, including high densities of TILs, MMR deficiency, and EBV positivity, but was not a prognostic factor.