title: Interferon response factor 3 is crucial to poly-I:C induced NK cell activity and control of B16 melanoma growth.
abstract: Interferon Response Factor 3 (IRF3) induces several NK-cell activating factors, is activated by poly-I:C, an experimental cancer therapeutic, but is suppressed during many viral infections. IRF3 Knockout (KO) mice exhibited enhanced B16 melanoma growth, impaired intratumoral NK cell infiltration, but not an impaired poly-I:C therapeutic effect due to direct suppression of B16 growth. IRF3 was responsible for poly-I:C decrease in TIM-3 expression by intratumoral dendritic cells, induction of NK-cell Granzyme B and IFN-γ, and induction of macrophage IL-12, IL-15, IL-6, and IRF3-dependent NK-activating molecule (INAM). Thus, IRF3 is a key factor controlling melanoma growth through NK-cell activities, especially during poly-I:C therapy.
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, United States.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Moore
authors.affiliation: Department of Oral Biology, University of Nebraska Medical Center, United States.
authors.forename: Phyllis M
authors.initials: PM
authors.lastname: Kumm
authors.affiliation: School of Biological Sciences, University of Nebraska-Lincoln, United States; Nebraska Center for Virology, University of Nebraska-Lincoln, United States.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Brown
authors.affiliation: Nebraska Center for Virology, University of Nebraska-Lincoln, United States; Department of Oral Biology, University of Nebraska Medical Center, United States. Electronic address: tpetro@unmc.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Petro
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005434:Flow Cytometry; D007369:Interferon Inducers / Q000494:pharmacology; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011070:Poly I-C / Q000494:pharmacology
chemical_list: D007369:Interferon Inducers; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D011070:Poly I-C
keywords: Cytokines; IRF3; Melanoma; NK-cells; Poly-I:C