Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8alpha+ dendritic cells

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-b was produced by CD11c(+) cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-a/bR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8a(+) 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 CD8alfa(+) DCs.Fil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University Of Chicago; Estados UnidosFil: Kacha, Aalok K. . University Of Chicago; Estados UnidosFil: Kline, Justin . University Of Chicago; Estados UnidosFil: Woo, Seng Ryong . University Of Chicago; Estados UnidosFil: Kranz, David M. . University Of Illinois; Estados UnidosFil: Murphy, Kenneth M. . Washington University in St. Louis; Estados UnidosFil: Gajewski, Thomas F. . University Of Chicago; Estados Unido