2024 World Conference on Lung Cancer (WCLC) - Posters-P1.02B.01 Mirnome Functional Profiling of Non-Small Cell Lung Cancer Identified New Mechanisms of PD-L1 Regulation

P1.02B.01 Mirnome Functional Profiling of Non-Small Cell Lung Cancer Identified New Mechanisms of PD-L1 Regulation

Pdf Summary

This study explored miRNA functionality in regulating PD-L1 expression in Non-Small Cell Lung Cancer (NSCLC), revealing novel mechanisms that could influence immunotherapy outcomes. Immune checkpoint inhibitors, particularly anti-PD-(L)-1 antibodies, have proven effective for NSCLC treatment. However, the 3' UTR disruption in the PD-L1 gene across various tumors results in its stabilization and overexpression, impacting treatment responses.<br /><br />Researchers undertook extensive miRNA profiling using a high-throughput human miRNA lentiviral library (shMIMIC) in NSCLC cells. This approach identified a miRNA-PD-L1 axis linking interferon (IFN) signaling to the miRNA miR-455-5p, which modulates PD-L1 expression and contributes to resistance to immune checkpoint therapy (ICT). Specifically, miR-455-5p was shown to affect genes central to IFN response, with a strong correlation between miR-455-5p levels and PD-L1 expression in NSCLC samples and cell lines.<br /><br />The study identified 250 candidate miRNAs linked to PD-L1, with 15 miRNAs overlapping with those differentially expressed in lung adenocarcinoma (LUAD) samples characterized by high versus low PD-L1 expression. IFN treatment of LUAD cells, followed by miRNA sequencing, highlighted miRNAs regulated by IFN that are implicated in PD-L1 regulation.<br /><br />The findings suggest that miRNA pathways connecting IFN signaling to PD-L1 modulation could be crucial in developing predictive biomarkers for assessing response to immunotherapy and understanding resistance mechanisms. This research opens avenues for enhancing the efficacy of cancer treatments by targeting these newly identified miRNA mechanisms.

Asset Subtitle

Fabrizio Bianchi

Meta Tag

Speaker Fabrizio Bianchi

Topic Tumor Biology – Preclinical Biology

Keywords

miRNA

PD-L1

NSCLC

immunotherapy

immune checkpoint inhibitors

miR-455-5p

interferon signaling

3' UTR disruption

biomarkers

cancer treatment