IL4I1 enhances PD-L1 expression through JAK/STAT signaling pathway in lung adenocarcinoma

Lung adenocarcinoma (LUAD) is the major type of lung cancer and is one of the deadliest cancers worldwide. IL4I1, as a gene associated with unsatisfactory prognosis, is involved in tumor immune escape, but its immune regulatory mechanism in LUAD is limited. Bioinformatics analysis was applied to analyze the differentially expressed mRNAs and enriched signaling pathways in LUAD tissue. Quantitative real-time polymerase chain reaction (qRT-PCR) was manipulated to test IL4I1 expression. We carried out several methods to examine cell functions: CCK-8 to measure LUAD cell proliferation; flow cytometry to determine cell apoptosis; Western blot to assess the expression of JAK/STAT pathway-related proteins and PD-L1; T cell cytotoxicity assay to evaluate the effect of IL4I1 on the immune escape of LUAD cells. Through bioinformatics analysis, IL4I1 was verified to be highly expressed in LUAD tissue, participate in the modulation of JAK/STAT signaling pathway, and be positively associated with CD274 (PD-L1) expression. Cell function experiments indicated that silencing IL4I1 notably repressed LUAD cell proliferation and induced apoptosis. IL4I1 silence would block JAK/STAT signaling pathway, but this effect could be reversed by RO8191 activator treatment. Moreover, IL4I1 silence suppressed PD-L1 expression and facilitated T cell cytotoxicity, while its inhibitory impact on PD-L1 expression and immune escape of LUAD cells could be reversed by atezolizumab treatment. Overall, we confirmed that IL4I1 promoted the malignant cell behaviors and immune escape of LUAD through JAK/STAT signaling pathway. IL4I1 has the potential to be a diagnostic biomarker for LUAD.

Automated summary

IL4I1 is highly expressed in LUAD tissue and involved in the regulation of JAK/STAT signaling pathway. Silencing IL4I1 inhibits LUAD cell proliferation and promotes apoptosis. Silencing IL4I1 also suppresses PD-L1 expression and enhances T cell cytotoxicity. Overall, IL4I1 promotes malignant cell behaviors and immune escape in LUAD through the JAK/STAT signaling pathway.