Potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells

Abstract Interferon (IFN)-λs (IL-28A/IL-28B/IL-29) classified as type III IFNs, are the latest members identified of the interferon family. As with type I IFNs such as IFN-α, type III IFNs share antiviral and antitumor activity and may have fewer side effects due to a more selective receptor distribution. Therefore, type III IFNs may be clinically useful for human viral and malignant diseases. Here we demonstrate the potential anti-tumor effect of IFN-λ2 (IL-28A) against human lung cancer cells. All lung cancer cell lines that we examined expressed both IFN-λ receptors (IL-28R1 and IL-10R2). Lung cancer cells with epidermal growth factor receptor (EGFR) mutations were more sensitive to IFN-λ2 treatment compared with cells with KRAS mutations. HCC827 cells with an EGFR mutation treated with IFN-λ2 underwent growth suppression and apoptotic cell death by STAT1 phosphorylation. Administration of neutralizing antibodies to IFN-λ inhibited caspase-3/7 activity induced by IFN-λ2. Finally, in vivo luminescent imaging also demonstrated the anti-tumor effect of IFN-λ2 in a cancer cell transplant animal model. Taken together, IFN-λ2 would be a new therapeutic agent for clinical lung cancers with EGFR mutations.