title: Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells.
abstract: Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c(+) cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α(+) dendritic cells, which were demonstrated to be essential using Batf3(-/-) mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α(+) DCs.
authors.affiliation: Department of Pathology and Department of Medicine, Section of Hematology/Oncology, the University of Chicago, Chicago, IL, USA.
authors.forename: Mercedes B
authors.initials: MB
authors.lastname: Fuertes
authors.forename: Aalok K
authors.initials: AK
authors.lastname: Kacha
authors.forename: Justin
authors.initials: J
authors.lastname: Kline
authors.forename: Seng-Ryong
authors.initials: SR
authors.lastname: Woo
authors.forename: David M
authors.initials: DM
authors.lastname: Kranz
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008207:Lymphatic Metastasis / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D050794:STAT1 Transcription Factor