Abstract

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.

Highlights

  • According to Global Cancer Statistics 2020, lung cancer is the most common cause of cancer-related deaths worldwide, whose incidence rate ranks second

  • Based on the TIMER2.0, we quantified the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME) of the The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD) and TCGA-lung squamous cell carcinoma (LUSC) cohorts, including three types related to adaptive immunity: B cell, CD4 T cell, and CD8 T cell, as well as three types related to innate immunity: macrophage, myeloid dendritic cell (DC1), and neutrophil

  • B cell and DC1 were significantly related to the survival of LUAD patients, whereas

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Summary

Introduction

According to Global Cancer Statistics 2020, lung cancer is the most common cause of cancer-related deaths worldwide, whose incidence rate ranks second (second only to breast cancer). The unoptimistic mortality rate makes lung cancer patients full of doubts about how long they can live, which is a problem that clinicians cannot avoid and facilitates the construction of various prognostic signatures (He and Zuo, 2019; Zuo et al, 2019). Adhering to the principles of personalized medicine and precision medicine, which lung cancer patients might benefit more from immunotherapy, is a vital issue that urgently needs to be solved. It is crucial to identify new targets or signatures that could predict both prognosis and immunotherapy efficacy of lung cancer patients

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