Identification immunophenotyping of lung adenocarcinomas based on the tumor microenvironment. Issue 11 (7th February 2020)

• Record Type: Journal Article
• Authors: Tan, Qilong; Huang, Yue; Deng, Kui; Lu, Mingliang; Wang, Liuying; Rong, Zhiwei; Zhao, Weiwei; Li, Shuang; Xu, Zhenyi; Fan, Lijun; Li, Kang; Li, Zhenzi
• Is Part Of: Journal of cellular biochemistry. Volume 121:Issue 11(2020)
• Page Start: 4569
• Page End: 4579
• Publication Date: 2020-02-07
• Subjects: immune checkpoint blockade -- immunophenotype -- lung adenocarcinoma -- tumor immune microenvironment; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29675
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: 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. Abstract : In this study, we comprehensively analyzed gene expression profiles of total 1089 lung adenocarcinomas (LUAD) and identified and validated independently an unreported immunophenotype in LUAD, and further subdivided this into two subtypes based on the tumor microenvironment, namely the Active Immune Class and Exhausted Immune Class. The Active Immune Class showed a better capacity to predict response to immunotherapy through validation with a melanoma cohort treated with anti‐programmed death‐1 agents. This study will provide a reasonable reference for the allocation of immunotherapy to specific populations.