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

Mercedes B Fuertes | Aalok K Kacha | Justin Kline | Seng-Ryong Woo | David M Kranz | Kenneth M Murphy | Thomas F Gajewski
The Journal of experimental medicine | 2011

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.

Pubmed ID: 21930765

Research resources used in this publication

None found

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P01 CA097296
  • Agency: Wellcome Trust, United Kingdom
  • Agency: NCI NIH HHS, United States
    Id: P01 CA97296

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