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, Mercedes B Fuertes, Aalok K Kacha, Justin Kline, Seng-Ryong Woo, David M Kranz, Kenneth M Murphy, Thomas F Gajewski
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.
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References
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