Tobacco extracts promote PD-L1 expression and enhance malignant biological differences via mTOR in gefitinib-resistant cell lines.

ABSTRACT

BACKGROUND: The aim of this study was to investigate whether tobacco extracts could regulate PD-L1 expression and enhance malignant biological differences in gefitinib-resistant cell lines. METHODS: We constructed gefitinib-resistant cells and observed the biological differences in gefitinib-resistant cells. The cells were stimulated with medium containing 5% volume of tobacco extract, and the change in PD-L1 expression and the mammalian target of rapamycin (mTOR) and p-mTOR expression in gefitinib-resistant cells treated with tobacco extracts was observed. We discussed the relationship between PD-L1 and mTOR. RESULTS: Tobacco extracts could promote PD-L1 expression in the cell line. Western blot analysis showed that mTOR and p-mTOR were significantly enhanced in gefitinib-resistant cell lines cultured in the tobacco extracts. The mTOR signaling pathway was involved in PD-L1 expression and in regulating the expression of cytokines IL-6 and IL-23. In addition, the tobacco extracts could promote macrophage migration via mTOR/IL-6. CONCLUSIONS: PD-L1 can transmit inhibitory signals and reduce the proliferation of CD8 + T cells in lymph nodes. Tobacco extracts upregulate PD-L1 expression via mTOR/IL-6. These results imply that lung cancer patients should not smoke and stay away from a smoke environment.