2023 World Conference on Lung Cancer (Posters)-P1.08. Hyper-Interferon Sensitive Influenza Virus Induces Immune Activation and Overcomes Resistance to Anti-PD-1 in Murine NSCLC

P1.08. Hyper-Interferon Sensitive Influenza Virus Induces Immune Activation and Overcomes Resistance to Anti-PD-1 in Murine NSCLC - PDF(Abstract)

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This study investigates the use of a live attenuated influenza viral vaccine known as 'hyper-interferon sensitive (HIS)' to overcome resistance to immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC). The researchers focused on two central hallmarks of ICI resistance: T cell exclusion from the tumor and dysfunction of the T cell compartment within the tumor microenvironment (TME). They found that loss of LKB1 in KRAS-mutant NSCLC drives resistance to ICI by suppressing STING, which results in interferon (IFN) signaling dysregulation. Leveraging the IFN pathway through virotherapy with HIS was explored as a potential treatment strategy. The HIS virus induced robust IFN responses in NSCLC cells and showed superior efficacy compared to wild-type influenza in murine models of NSCLC. Intratumoral administration of the HIS virus led to type 1 IFN response, T cell and natural killer (NK) infiltration and activation, and synergistic tumor inhibition when combined with anti-PD-1. Successful eradication of tumors with the combination therapy led to long-lasting anti-tumor immunity. The study concludes that HIS virotherapy induces hyper-IFN secretion in the TME and sensitizes immune-resistant NSCLC to ICI. The findings support further clinical evaluation of HIS virotherapy as a potential treatment for NSCLC that does not respond to current ICI therapies.

Asset Subtitle

Ramin Salehi-rad

Meta Tag

Speaker Ramin Salehi-rad

Topic Tumor Biology: Translational Biology - Drug Resistance

Keywords

live attenuated influenza viral vaccine

immune checkpoint inhibitors

non-small cell lung cancer (NSCLC)

T cell exclusion

tumor microenvironment (TME)

LKB1

KRAS-mutant NSCLC

interferon (IFN) signaling dysregulation

virotherapy

anti-PD-1