Soo Ross A, Kim Hye Ryun, Asuncion Bernadette Reyna, Fazreen Zul, Omar Mohamed Feroz Mohd, Herrera Maria Cynthia, Yun Lim Joey Sze, Sia Grace, Soong Richie, Cho Byoung-Chul
Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore; School of Surgery, University of Western Australia, Perth, Australia; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Division of Medical Oncology, Yonsei Cancer Center, Seoul, South Korea.
Lung Cancer. 2017 Mar;105:17-22. doi: 10.1016/j.lungcan.2017.01.008. Epub 2017 Jan 15.
To characterize the expression of PD-L1, PD-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin and mucin-domain containing-3 (TIM3) in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC).
Samples from 90 patients with newly diagnosed advanced stage NSCLC harboring EGFR mutations and treated with first line EGFR tyrosine kinase inhibitors (TKI) within 3 months of diagnosis were stained for CTLA-4, PD-L1, PD-1, TIM-3 and CD3 expression by immunohistochemistry.
PD-L1 was present in at least 1% of immune and tumor cells in 44% and 59% of samples, respectively. In multivariate analysis, increased CD3 immune shaped cell (ISC) counts (HR 2.805, p=0.034) and high PD-L1 tumor H-score (HR 3.805, p=0.022) was associated with a shorter progression free survival and high CTLA-4 ISC counts was associated with borderline overall survival significance (HR 1.054, p=0.061).
Tumor PD-L1 expression was significantly associated with a shorter PFS whereas immune cell CTLA-4 may be prognostic for OS. Our findings support the ongoing development of CTLA-4 and PD1/PD-L1 inhibitors in this important molecularly defined subset of lung adenocarcinoma.
对表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）中程序性死亡配体1（PD-L1）、程序性死亡受体1（PD-1）、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和含T细胞免疫球蛋白和粘蛋白结构域3（TIM3）的表达进行特征分析。
对90例新诊断的晚期NSCLC患者的样本进行研究，这些患者携带EGFR突变，并在诊断后3个月内接受一线EGFR酪氨酸激酶抑制剂（TKI）治疗。通过免疫组织化学对样本进行CTLA-4、PD-L1、PD-1、TIM-3和CD3表达染色。
分别在44%和59%的样本中，至少1%的免疫细胞和肿瘤细胞中存在PD-L1。多因素分析显示，CD3免疫塑形细胞（ISC）计数增加（风险比[HR]2.805，p=0.034）和高PD-L1肿瘤H评分（HR 3.805，p=0.022）与无进展生存期缩短相关，而高CTLA-4 ISC计数与总生存期具有临界显著性相关（HR 1.054，p=0.061）。
肿瘤PD-L1表达与较短的无进展生存期显著相关，而免疫细胞CTLA-4可能对总生存期具有预后价值。我们的研究结果支持在这一重要的分子定义的肺腺癌亚组中持续开发CTLA-4和PD1/PD-L1抑制剂。
