Abstract
IntroductionPrevious clinical investigations have demonstrated that patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation have moderate responses to programmed cell death-1 and it's ligand-1 (PD-1/PD-L1) inhibitors, while some patients who failed EGFR-tyrosine kinase inhibitor (TKI) therapy could benefit from immunotherapy. As a result, we have explored alterations in the tumor immune microenvironment (TIME) before and after EGFR-TKI treatment to detect the chances and proper timing of immunotherapy among patients. MethodsWe identified 16 paired tissue samples pre- and post-EGFR-TKI treatment. Sections 4 μm thick were utilized to evaluate CD8, PD-L1, PD-1, LAG-3, and TIM-3 expressions by multiplexed fluorescent immunohistochemical staining. Five to ten representative original multispectral images of each sample were employed in the analysis. ResultsPatients with positive CD8 + T-cell infiltration accounted for 37.5 % at baseline. Positive expression of PD-L1, PD1, LAG-3, and TIM-3 cells were observed in seven (43.8 %), four (25 %), one (6.25 %) and five (31.25 %) of the patients, respectively. PD-1 expression and infiltration of CD8+PD-1+-exhausted T cells increased significantly in patients with EGFR L858R mutation compared to patients with EGFR 19DEL. Patients who acquired T790 M after TKI treatment had less infiltrations of CD8+PD-1+ T cells and CD8+TIM-3+ T cells in the TIME at baseline. Positive expression of checkpoint proteins—including PD-1, TIM-3, and LAG-3—significantly correlated with shorter progression-free survival. LAG-3 was significantly upregulated after TKI treatment (p = 0.003), while other checkpoint proteins remained stationary. ConclusionThe present study is the first work to report LAG-3 upregulation after EGFR-TKI failure in advanced NSCLC, which proposed novel insights for rational use of LAG-3 inhibitors in advanced NSCLC patients with EGFR mutation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.