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Abstract
Lung tissue is abundant with immune cells that form a powerful first defense against exotic particles and microbes. The malignant phenotype of lung adenocarcinoma (LUAD) is defined not only by intrinsic tumor cells but also by tumor-infiltrating immune cells (TIICs) recruited to the immune microenvironment. Understanding more about the immune microenvironment of LUAD could function in sorting out patients more likely with high risk and benefit from immunotherapy. Twenty-two types of TIICs were estimated based on large public LUAD cohorts from the TCGA and GEO datasets using the CIBERSORT algorithm. Then principal component analysis (PCA), meta-analysis, and single-sample gene set enrichment analysis (ssGSEA) were used to measure and evaluate the specific immune responses and relative mechanisms. Moreover, an immunoscore model based on the percent of immune cells was constructed via the univariate and multivariate Cox regression models, which provided an in-depth overview of the LUAD immune microenvironment and shed light on the immune regulatory mechanism. The differential expression genes (DEGs) were acquired based on the immunoscore model, and prognostic immune-related genes were further identified. GSEA and the protein–protein interaction network (PPI) further revealed that these genes were mostly enriched in many immune-related biological processes. It is hoped that this immune landscape could provide a more accurate understanding for LUAD development and tumor immune therapy.
Highlights
Lung adenocarcinoma (LUAD), a dominating subtype of non-small-cell lung cancer, is acknowledged and regarded as one of the most leading cause of cancer-related mortality worldwide, with a five-year survival rate of only 22.1% [1]
Setting P < 0:05 as the cut-off, we deeply explored the composition of tumor-infiltrating immune cells (TIICs) in the LUAD to implement more convincing conclusions
After applying data filter criteria, 564 annotated lung adenocarcinoma samples with immune cell fraction were available for further analyses
Summary
Lung adenocarcinoma (LUAD), a dominating subtype of non-small-cell lung cancer, is acknowledged and regarded as one of the most leading cause of cancer-related mortality worldwide, with a five-year survival rate of only 22.1% [1]. IFN response, immune checkpoints, HLA, cytokine, inflammation factor, and adoptive cell transplantation have been proven to make a great contribution in the progression of lung cancer. Immunotherapy, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) checkpoint inhibitors and CTLA4, concentrates on revitalizing immunologic cells to release molecular components to defend against cancer cell in the tumor microenvironment. It has been studied that pembrolizumab and nivolumab exhibited a surprising antitumor activity in advanced NSCLC with better overall survival (OS) and progression-free survival (PFS) than traditional second-line chemotherapy [3, 4].
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