Tan Qilong, Huang Yue, Deng Kui, Lu Mingliang, Wang Liuying, Rong Zhiwei, Zhao Weiwei, Li Shuang, Xu Zhenyi, Fan Lijun, Li Kang, Li Zhenzi
Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin, China.
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.
J Cell Biochem. 2020 Nov;121(11):4569-4579. doi: 10.1002/jcb.29675. Epub 2020 Feb 7.
The tumor immune microenvironment is heterogeneous, and its impact on treatment responses is not well understood. It is still a challenge to analyze the interaction between malignant cells and the tumor microenvironment to apply suitable immunotherapy in lung adenocarcinoma. We performed the nonnegative matrix factorization method to 513 messenger RNA expression profiles of lung adenocarcinomas (LUADs) from The Cancer Genome Atlas (TCGA) to obtain an immune-related expression pattern. Subsequently, we characterized the immune-related gene signatures and clinical and survival characteristics. We used 576 patients from Gene Expression Omnibus to confirm our findings. Of the patients in the training cohort, 51% had a high immune enrichment score, high expression of immune cell signaling, cytolytic activity, and interferon (IFN)-related signatures (all P < .05). We denoted these as the Immune Class. We further subdivided the Immune Class into two subclasses based on the tumor microenvironment. These were denoted the Active Immune Class and Exhausted Immune Class. The former showed significant IFN, T-cells, M1 macrophage signatures, and better prognosis (all P < .05), while the latter presented an exhausted immune response with activated stromal enrichment, M2 macrophage signatures, and immunosuppressive factors such as WNT/transforming growth factor-β (all P < .05). Furthermore, we predicted the response of our immunophenotypes to immunological checkpoint inhibitors (P < .05). Our findings provide a novel insight into the immune-related state of LUAD and can identify the patients who will be receptive to suitable immunotherapeutic treatments.
肿瘤免疫微环境具有异质性，其对治疗反应的影响尚未得到充分理解。分析恶性细胞与肿瘤微环境之间的相互作用，以便在肺腺癌中应用合适的免疫疗法仍是一项挑战。我们对来自癌症基因组图谱（TCGA）的513个肺腺癌（LUAD）信使核糖核酸表达谱进行了非负矩阵分解方法，以获得免疫相关的表达模式。随后，我们对免疫相关基因特征以及临床和生存特征进行了表征。我们使用来自基因表达综合数据库的576名患者来证实我们的发现。在训练队列中的患者中，51%具有高免疫富集评分、免疫细胞信号传导、细胞溶解活性和干扰素（IFN）相关特征的高表达（所有P < 0.05）。我们将这些患者定义为免疫类。我们根据肿瘤微环境将免疫类进一步细分为两个亚类。这些亚类分别被定义为活跃免疫类和耗竭免疫类。前者显示出显著的IFN、T细胞、M1巨噬细胞特征，且预后较好（所有P < 0.05），而后者呈现出具有激活的基质富集、M2巨噬细胞特征以及WNT/转化生长因子-β等免疫抑制因子的耗竭免疫反应（所有P < 0.05）。此外，我们预测了我们的免疫表型对免疫检查点抑制剂的反应（P < 0.05）。我们的发现为LUAD的免疫相关状态提供了新的见解，并能够识别出适合接受免疫治疗的患者。
