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-b 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.

Automated summary

In this study, the researchers investigated the different roles of tumor-infiltrating dendritic cells (DCs) in anti-tumor immunity. By comparing spontaneously regressing and progressing tumors, they found that tumor-reactive CD8+ T cells were lost in progressing tumors but preserved in regressing tumors. They also identified a specific type of DCs (ISG(+) DCs) in regressing tumors that activated CD8+ T cells and played an important role in presenting tumor-derived antigens. Furthermore, they showed that exogenous IFN-b stimulation could restore the lost anti-tumor immunity in progressing tumors. These findings suggest that targeting this functional DC state may be a potential approach for the treatment of human diseases.