2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03D.11 Association Between Plasminogen Activator Inhibitor-1 & Tolerance Against Anti-PD-1 Antibody in Non-Small Cell Lung Cancer

P1.03D.11 Association Between Plasminogen Activator Inhibitor-1 & Tolerance Against Anti-PD-1 Antibody in Non-Small Cell Lung Cancer

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The study investigates the role of plasminogen activator inhibitor-1 (PAI-1) in mediating tolerance to anti-PD-1 (aPD-1) antibody treatment in non-small cell lung cancer (NSCLC). PAI-1 is a glycoprotein that influences drug-tolerant cancer cells (DTCs) and is associated with epithelial-mesenchymal transition (EMT), promoting tumor regrowth post-treatment. The research identifies that PAI-1 contributes to aPD-1 antibody tolerance by increasing tumor-associated macrophages (TAMs) and PD-L1 expression while decreasing tumor-infiltrating lymphocytes (TILs), thereby creating an immunosuppressive tumor immune microenvironment (TIME).<br /><br />TM5614, a PAI-1 inhibitor, was found to improve the TIME in aPD-1 treated NSCLC cells, suggesting its potential in overcoming drug tolerance. This study presents TM5614 as a therapeutic measure to target PAI-1 and mitigate resistance to immunotherapy. Similar outcomes were observed in KLN205 cell subcutaneous tumor models, reinforcing the findings across different experimental settings.<br /><br />Overall, this research highlights PAI-1 as a critical factor in the acquisition of tolerance to aPD-1 treatment through EMT and TIME modulation. It proposes PAI-1 as a promising therapeutic target, aiming to enhance the effectiveness of immunotherapies like aPD-1 antibodies, especially for those with advanced NSCLC experiencing resistance. This approach could potentially lead to improved prognosis and management of NSCLC, addressing the significant issue of cancer cell tolerance to frontline immunotherapeutic treatments. The findings make a significant contribution by recognizing PAI-1's role and presenting an inhibitor that can improve the efficiency of existing cancer therapies.

Asset Subtitle

Masahiko Sumii

Meta Tag

Speaker Masahiko Sumii

Topic Tumor Biology – Translational Biology

Keywords

PAI-1

anti-PD-1

NSCLC

drug tolerance

tumor immune microenvironment

TM5614

immunotherapy resistance

epithelial-mesenchymal transition

tumor-associated macrophages

tumor-infiltrating lymphocytes