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

J Exp Med. 2011 Sep 26;208(10):2005-16. doi: 10.1084/jem.20101159. Epub 2011 Sep 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • Humans
  • Immunity, Innate / immunology
  • Interferon Type I / immunology*
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / immunology
  • Lymphocyte Subsets / immunology*
  • Melanoma / immunology*
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • Signal Transduction / immunology*

Substances

  • Interferon Type I
  • STAT1 Transcription Factor