Toll-Like Receptor 7 Enhances the Inhibition of Natural Killer Cells on Non-Small Cell Lung Cancer Cell Proliferation by Upregulating the Spliced Form of X-box Binding Protein 1

Abstract

Background: Toll-like receptor (TLR) 7 suppresses non-small cell lung cancer (NSCLC) progression and enhances natural killer (NK) cell function. Therefore, this study aimed to elucidate the underlying mechanism of TLR7 enhancing the influences of NK cells on the viability and proliferation of NSCLC cells. Methods: Identification of NK cells was conducted using flow cytometry. The expression levels of TLR7 and spliced form of x-box binding protein 1 (XBP1s) in lung adenocarcinoma, NK cells, and NSCLC cells were assessed through online website, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blot. After overexpressing or silencing TLR7 in NK cells, their impact on the activity and proliferation (immunofluorescence) of NSCLC cells was determined. Furthermore, after transfecting NSCLC cells with TLR7 overexpression plasmid and short hairpin RNA targeting XBP1s (shXBP1s), the colony formation capabilities of NSCLC cells and their sensitivity to NK cells were evaluated. Results: NK cells overexpressing TLR7 exhibited increased viability, high XBP1s expression, and enhanced inhibitory effect on the viability and proliferation of NSCLC cells (p < 0.01). Furthermore, TLR7-overexpressing NSCLC cells demonstrated stronger sensitivity to NK cells, but this effect was reversed upon XBP1s silencing (p < 0.05). The vitality and proliferation of NSCLC cells were inhibited by TLR7 overexpression and/or XBP1s silencing (p < 0.05). TLR7 or XBP1s expression in NSCLC cells was upregulated by TLR7 overexpression or XBP1s silencing (p < 0.05). Conclusion: This study confirmed that TLR7 enhances the inhibitory effect of NK cells on the viability and proliferation of NSCLC cells by upregulating XBP1s expression.