title: 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.
authors.affiliation: Department of General Thoracic Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tezuka
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Endo
authors.forename: Aya
authors.initials: A
authors.lastname: Matsui
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sato
authors.forename: Katsuyo
authors.initials: K
authors.lastname: Saito
authors.forename: Kentaro
authors.initials: K
authors.lastname: Semba
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007378:Interleukins / Q000494:pharmacology* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018121:Receptors, Cytokine / Q000378:metabolism; D017471:Receptors, Interferon; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000095022:Interferon Lambda
chemical_list: D000970:Antineoplastic Agents; D007378:Interleukins; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D050794:STAT1 Transcription Factor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579640:IFNLR1 protein, human; C494079:STAT1 protein, human