The Prognosis and Immune Checkpoint Blockade Efficacy Prediction of Tumor-Infiltrating Immune Cells in Lung Cancer

• DOI: 10.3389/fcell.2021.707143
• Publication Date: 2021-08-03T16:27:20Z
• Authors: Xiangzheng Liu; Xueqian Shang; Jian Li; Shijie Zhang
• Keywords: Pulmonary and Respiratory Medicine; Cancer Immunoediting; Mechanisms and Implications of Ferroptosis in Cancer; QH301-705.5; Immunology; Cancer research; Adenocarcinoma; Gene; Biochemistry; Cancer Immunotherapy; Cell and Developmental Biology; 03 medical and health sciences; Health Sciences; Tumor Microenvironment; Genetics; Biology (General); Biology; Cancer; Immunology and Microbiology; B cell; 0303 health sciences; Macrophage Activation and Polarization; FOS: Clinical medicine; Life Sciences; myeloid dendritic cell; immune checkpoint blockade; Immune Checkpoint Blockade; 3. Good health; lung cancer; Immune system; Oncology; Tumor microenvironment; FOS: Biological sciences; KEGG; Medicine; Biomarkers for Immunotherapy; prognosis; Immunotherapy; Immune checkpoint; Gene expression; Lung cancer; Transcriptome

BackgroundsThe high morbidity and mortality of lung cancer are serious public health problems. The prognosis of lung cancer and whether to apply immune checkpoint blockade (ICB) are currently urgent problems to be solved.MethodsUsing R software, we performed Kaplan–Meier (K-M) analysis, Cox regression analysis, functional enrichment analysis, Spearman correlation analysis, and the single-sample gene set enrichment analysis.ResultsOn the Tumor IMmune Estimation Resource (TIMER2.0) website, we calculated the abundance of tumor-infiltrating immune cells (TIICs) of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. B cell and myeloid dendritic cell (DC1) were independent prognostic factors for LUAD and LUSC patients, respectively. Enrichment analysis confirmed that genes highly related to B cell or DC1 were closely related to the immune activation of lung cancer patients. In terms of adaptive immune resistance markers, CD8A, CD8B, immunomodulators (immunostimulants, major histocompatibility complex, receptors, and chemokines), immune-related pathways, tumor microenvironment score, and TIICs, high B cell/DC1 infiltration tissue was inflamed and immune-activated and might benefit more from the ICB. Genes most related to B cell [CD19, toll-like receptor 10 (TLR10), and Fc receptor-like A (FCRLA)] and DC1 (ITGB2, LAPTM5, and SLC7A7) partially clarified the roles of B cell/DC1 in predicting ICB efficacy. Among the 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, there were three and four KEGG pathways, which partially explained the molecular mechanisms by which B cell and DC1 simultaneously predicted the prognosis and efficacy of immunotherapy, respectively. Among five immune subtypes, the abundance of B cell/DC1 and expression of six hub genes were higher in immune C2, C3, and C6.ConclusionB cell and DC1 could predict the prognosis and ICB efficacy of LUAD and LUSC patients, respectively. The six hub genes and seven KEGG pathways might be novel immunotherapy targets. Immune C2, C3, and C6 subtypes of lung cancer patients might benefit more from ICB therapy.