Toll-Like Receptor 4 and 8 are Overexpressed in Lung Biopsies of Human Non-small Cell Lung Carcinoma

Lung cancer is the leading cause of cancer death worldwide which includes two main types of carcinoma distinguished in non-small cell lung cancer (NSCLC) involving epithelial cells, and small cell lung cancer (SCLC) affecting neuronal cells and hormone secreting cells. Studies have shown a causal link between inflammation/innate immunity and onset of NSCLC. The present study aimed to evaluate the expression of Toll-like receptors (TLRs) 4 and TLR8 in peripheral blood mononuclear cells (PBMC) and in lung tissues of patients with NSCLC, useful for future prognostic tools for NSCLC.

Patients surgically treated for NSCLC with anatomical resections and patients with benign disease were enrolled. The expression levels of TLR4 and TLR8 were determined by real time PCR and by immunohistochemical analysis in PBMC and in lung tissues, respectively. A preliminary in silico analysis including 1194 arrays from healthy and cancer tissues were extracted by Genevestigator database. The association between TLRs gene expression and survival outcome was also investigated.

Bioinformatics analysis revealed that downregulation of TLR4 and TLR8 positively impacts the survival in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). However, no significant differences in TLR4 and TLR8 gene expression between case and control groups were observed in PBMC. A positive correlation was found in their expression levels. Interestingly, immunohistochemical analysis showed that the levels of TLR4 and TLR8 were higher in the lung tissues of patients with NSCLC than in the control group in terms of staining intensity and positive cells.

Albeit the precise role of TLRs is not fully defined, this study identified the potential involvement of TLR4 and TLR8 in the pathogenesis of NSCLC. Our data led us to hypothesize their potential role in overall survival which deserves to be explored further to establish whether TLR4 and TLR8 can represent positive prognostic indicators of disease in NSCLC.