Type I interferon activates MHC class I-dressed CD11b conventional dendritic cells to promote protective anti-tumor CD8 T cell immunity.

Tumor-infiltrating dendritic cells (DCs) assume varied functional states that impact anti-tumor immunity. To delineate the DC states associated with productive anti-tumor T cell immunity, we compared spontaneously regressing and progressing tumors. Tumor-reactive CD8 T cell responses in Batf3 mice lacking type 1 DCs (DC1s) were lost in progressor tumors but preserved in regressor tumors. Transcriptional profiling of intra-tumoral DCs within regressor tumors revealed an activation state of CD11b conventional DCs (DC2s) characterized by expression of interferon (IFN)-stimulated genes (ISGs) (ISG DCs). ISG DC-activated CD8 T cells ex vivo comparably to DC1. Unlike cross-presenting DC1, ISG DCs acquired and presented intact tumor-derived peptide-major histocompatibility complex class I (MHC class I) complexes. Constitutive type I IFN production by regressor tumors drove the ISG DC state, and activation of MHC class I-dressed ISG DCs by exogenous IFN-β rescued anti-tumor immunity against progressor tumors in Batf3 mice. The ISG DC gene signature is detectable in human tumors. Engaging this functional DC state may present an approach for the treatment of human disease.