title: Host STAT2/type I interferon axis controls tumor growth.
abstract: The role of STAT2 in mediating the antigrowth effects of type I interferon (IFN) is well-documented in vitro. Yet evidence of IFN-activated STAT2 as having tumor suppressor function in vivo and participation in antitumor immunity is lacking. Here we show in a syngeneic tumor transplantation model that STAT2 reduces tumor growth. Stat2(-/-) mice formed larger tumors compared to wild type (WT) mice. IFN-β treatment of Stat2(-/-) mice did not cause tumor regression. Gene expression analysis revealed a small subset of immunomodulatory genes to be downregulated in tumors established in Stat2(-/-) mice. Additionally, we found tumor antigen cross-presentation by Stat2(-/-) dendritic cells to T cells to be impaired. Adoptive transfer of tumor antigen specific CD8(+) T cells primed by Stat2(-/-) dendritic cells into tumor-bearing Stat2(-/-) mice did not induce tumor regression with IFN-β intervention. We observed that an increase in the number of CD4(+) and CD8(+) T cells in the draining lymph nodes of IFN-β-treated tumor-bearing WT mice was absent in IFN-β treated Stat2(-/-) mice. Thus our study provides evidence for further evaluation of STAT2 function in cancer patients receiving type I IFN based immunotherapy.
authors.affiliation: Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Chanyu
authors.initials: C
authors.lastname: Yue
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Marc Daryl
authors.initials: MD
authors.lastname: Tan Estioko
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Kotredes
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lopez-Otalora
authors.forename: Brendan A
authors.initials: BA
authors.lastname: Hilliard
authors.forename: Darren P
authors.initials: DP
authors.lastname: Baker
authors.forename: Stefania
authors.initials: S
authors.lastname: Gallucci
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gamero
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D003713:Dendritic Cells; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D016899:Interferon-beta / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C494080:Stat1 protein, mouse; C494085:Stat2 protein, mouse; D016899:Interferon-beta
keywords: STAT1; STAT2; antitumor; cross-presentation; dendritic cell; interferon; melanoma