奥希替尼治疗 EGFR 突变 NSCLC 中 PD-L1 表达的生存与分子机制转化研究

Highly expressed programmed death-ligand 1 (PD-L1) has been associated with poor clinical outcomes in patients with epidermal growth factor receptor ( EGFR )-mutated non-small cell lung cancer (NSCLC) receiving EGFR-tyrosine kinase inhibitors (TKIs).

However, the prognostic significance of PD-L1 expression in the context of first-line osimertinib treatment remains unclear. In this retrospective study, we analyzed 317 patients with EGFR -mutated stage III-IV lung adenocarcinoma treated with first-line osimertinib. Patients with high PD-L1 expression demonstrated significantly shorter progression-free survival and overall survival compared to those with low PD-L1 expression.

Transcriptomic analysis revealed upregulation of interferon-gamma (IFN- ) and interleukin (IL)-6/JAK/STAT3 pathways in high PD-L1 tumors. Flow cytometry identified an increased proportion of CD56 bright natural killer (NK) cells in patients with high PD-L1 expression. In vitro experiments further demonstrated that IFN- induces PD-L1 expression via STAT3 activation.

These findings provide evidence that baseline PD-L1 expression may serve as a prognostic biomarker for patients with EGFR -mutated NSCLC receiving first-line osimertinib and implicate the CD56 bright NK cell/IFN- /STAT3 axis in the regulation of PD-L1 expression.