School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
J Immunother Cancer. 2020 Feb;8(1). doi: 10.1136/jitc-2019-000110.
Increasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and the tumor microenvironment in non-small cell lung cancer (NSCLC). However, tumor immune infiltration-associated lncRNAs and their value in improving clinical outcomes and immunotherapy remain largely unexplored.
We developed a computational approach to identify an lncRNA signature (TILSig) as an indicator of immune cell infiltration in patients with NSCLC through integrative analysis for lncRNA, immune and clinical profiles of 115 immune cell lines, 187 NSCLC cell lines and 1533 patients with NSCLC. Then the influence of the TILSig on the prognosis and immunotherapy in NSCLC was comprehensively investigated.
Computational immune and lncRNA profiling analysis identified an lncRNA signature (TILSig) consisting of seven lncRNAs associated with tumor immune infiltration. The TILSig significantly stratified patients into the immune-cold group and immune-hot group in both training and validation cohorts. These immune-hot patients exhibit significantly improved survival outcome and greater immune cell infiltration compared with immune-cold patients. Multivariate analysis revealed that the TILSig is an independent predictive factor after adjusting for other clinical factors. Further analysis accounting for TILSig and immune checkpoint gene revealed that the TILSig has a discriminatory power in patients with similar expression levels of immune checkpoint genes and significantly prolonged survival was observed for patients with low TILSig and low immune checkpoint gene expression implying a better response to immune checkpoint inhibitor (ICI) immunotherapy.
Our finding demonstrated the importance and value of lncRNAs in evaluating the immune infiltrate of the tumor and highlighted the potential of lncRNA coupled with specific immune checkpoint factors as predictive biomarkers of ICI response to enable a more precise selection of patients.
越来越多的证据表明，长链非编码 RNA（lncRNA）在非小细胞肺癌（NSCLC）中的免疫调节和肿瘤微环境中具有功能相关性。然而，肿瘤免疫浸润相关的 lncRNA 及其在改善临床结局和免疫治疗中的价值在很大程度上仍未得到探索。
我们开发了一种计算方法，通过对 115 个免疫细胞系、187 个 NSCLC 细胞系和 1533 名 NSCLC 患者的 lncRNA、免疫和临床谱进行综合分析，确定了一个 lncRNA 特征（TILSig）作为 NSCLC 患者免疫细胞浸润的指标。然后，全面研究了 TILSig 对 NSCLC 预后和免疫治疗的影响。
计算免疫和 lncRNA 分析确定了一个由七个与肿瘤免疫浸润相关的 lncRNA 组成的 lncRNA 特征（TILSig）。TILSig 在训练和验证队列中显著将患者分为免疫冷组和免疫热组。与免疫冷患者相比，这些免疫热患者的生存结局显著改善，免疫细胞浸润程度更高。多变量分析显示，在调整其他临床因素后，TILSig 是一个独立的预测因素。进一步分析考虑 TILSig 和免疫检查点基因表明，TILSig 在免疫检查点基因表达水平相似的患者中具有区分能力，并且对于低 TILSig 和低免疫检查点基因表达的患者，生存时间显著延长，这表明对免疫检查点抑制剂（ICI）免疫治疗有更好的反应。
我们的研究结果表明，lncRNA 在评估肿瘤免疫浸润方面具有重要性和价值，并强调了 lncRNA 与特定免疫检查点因素相结合作为 ICI 反应预测生物标志物的潜力，以更精确地选择患者。
