Immune cell landscape analysis reveals prognostic immune cells and its potential mechanism in squamous cell lung carcinoma

Abstract

Background Squamous cell lung carcinoma (LUSC) was closely associated with smoking which was known to have a distant immunosuppression effect. In this study, we aimed to explore the relationship between immune cells and clinical outcomes of LUSC patients with smoking history. Methods The immune cell infiltration and RNA expression profiles of LUSC patients were collected from The Cancer Genome Atlas (TCGA). Then, the correlation between immune cell infiltration and clinical characteristics was explored. According to the level of immune cell infiltration, LUSC patients with smoking history were divided into high or low group to screen the differentially expressed lncRNAs and mRNAs. The prediction of target genes was performed by miRanda. Finally, the prognostic value of a certain signature was confirmed in an independent dataset. Results Higher abundance of tumor-infiltrating T follicular helper (Tfh) cells together with a lower abundance of resting memory CD4 T cells had been found in LUSC current reformed smokers for ≤15 years and current smoking patients. Moreover, Tfh cell infiltration was not only associated with better overall survival (OS) but also varied from different degrees of TNM stage. Low expression of lncRNA PWRN1 and its potential regulating genes DMRTB1, PIRT, APOBEC1, and ZPBP2 were associated with better OS. Combining PWRN1 and four regulating genes as a signature, patients with higher-level expression of the signature had shorter survival time in not only the TCGA but also in the GEO dataset. Conclusions It was found that Tfh cells presented higher infiltration in LUSC current reformed smokers for ≤15 years and current smokers, while resting memory CD4 T cells had lower infiltration. The signature consisting of PWRN1 as well as its predicted targeted mRNAs was dysregulated in different levels of Tfh cell infiltration and might indicate patients’ OS.

Integrated bioinformatics analyses identifying key transcriptomes correlated with prognosis and immune infiltrations in lung squamous cell carcinoma

“…The lung microenvironment promotes the carcinogenesis of LUSC, including inflammation, angiogenesis, immune modulation or inhibition, and response or resistance to therapies ( Altorki et al, 2019 ). Yongyong Wang et al demonstrated that immune cell infiltrations are associated with the prognosis in squamous cell lung carcinoma ( Wang and Guo, 2020 ). The immune landscape accurately provides the development and immunotherapy status of LUSC ( Zhao et al, 2020 ).…”

Role of Long Noncoding RNAs in Smoking-Induced Lung Cancer: An In Silico Study

“…For example, Wasén et al found that smoking induces the apoptosis of CD4 + T cells in patients with rheumatoid arthritis [ 38 ]. Furthermore, Wang and Guo found decreased infiltration of resting memory CD4 T cells and increased infiltration of follicular helper T cells in patients with lung squamous cell cancer who smoked or had quit smoking for less than 15 years [ 39 ]. The results of our study are consistent with those of these studies.…”

Clinicopathological implications of lncRNAs, immunotherapy and DNA methylation in lung squamous cell carcinoma: a narrative review

“…Tfh cells are reported to show more significant infiltration in current smokers and LUSC current reformed smokers who have been smoking for less than 15 years, whereas resting memory CD4 T cells had reduced infiltration. Tfh cell infiltration has been linked to a higher overall survival (OS) rate; however, the relationship varied depending on the TNM stage ( 118 ).…”