| First Author | Duong E | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 2 | Pages | 308-323.e9 |
| PubMed ID | 34800368 | Mgi Jnum | J:336191 |
| Mgi Id | MGI:6874634 | Doi | 10.1016/j.immuni.2021.10.020 |
| Citation | Duong E, et al. (2022) Type I interferon activates MHC class I-dressed CD11b(+) conventional dendritic cells to promote protective anti-tumor CD8(+) T cell immunity. Immunity 55(2):308-323.e9 |
| abstractText | 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-beta 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. |
