Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells

MB Fuertes, AK Kacha, J Kline, SR Woo… - Journal of Experimental …, 2011 - rupress.org
Journal of Experimental Medicine, 2011rupress.org
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 …
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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