The impact of tobacco exposure on tumor microenvironment and prognosis in lung adenocarcinoma by integrative analysis of multi-omics data

• Published in: International immunopharmacology 2021-12, Vol.101 (Pt B), p.108253-108253, Article 108253
• Main Authors: Lu, Xiaomin, Ma, Liang, Yin, Xuewen, Ji, Haoming, Qian, Ye, Zhong, Sixun, Yan, Aiting, Zhang, Yan
• Format: Article
• Language: English
• Subjects: A549 Cells; Adenocarcinoma; Adenocarcinoma - diagnosis; Adenocarcinoma - immunology; Adenocarcinoma - mortality; Algorithms; B-Lymphocyte Subsets - immunology; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers, Tumor - metabolism; Cancer; CD4 antigen; CD8 antigen; Computational Biology; Datasets as Topic; Exposure; Gene Expression Regulation, Neoplastic; Genomes; High-Throughput Nucleotide Sequencing; Humans; Immune checkpoint inhibitors; Immune status; Immunohistochemistry; Immunologic Memory; Immunological memory; Immunotherapy; Inhibitors; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lungs; Lymphocytes; Lymphocytes B; Lymphocytes T; Memory cells; Metastases; Microenvironment; Models, Statistical; Patients; PD-L1 protein; Phenotypes; Prediction models; Prognosis; Proteomics; RFscore; Smoking; Survival Analysis; T-Lymphocytes - immunology; Tobacco; Tobacco smoking; Tobacco Smoking - adverse effects; Tumor Microenvironment; Tumors
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108253

•Tobacco exposure impacts TME.•RFscore predicts OS in LUAD.•Tobacco exposure alters immune infiltration status. Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced lung adenocarcinoma and significantly improve treatment outcomes. The effect of tobacco smoking on the response of immune checkpoint inhibitors is somewhat diverging. Here, we assessed the impact of tobacco exposure on the tumor microenvironment and developed a feasible tool for predicting prognosis. Whole exon sequence data and the corresponding clinical information were downloaded from the Cancer Genome Atlas. The signature was developed by the Random Forest algorithm. CIBERSORTx online tool was used to estimate immune infiltration. Functional assays were performed to assess the roles of tobacco exposure in cancer cells. Immunohistochemistry (IHC) was performed to identify and validate the immune activation status. The TMB of lifelong non-smoker, current reformed smoker for over 15 years, current reformed smoker