| First Author | Sharma MD | Year | 2018 |
| Journal | Immunity | Volume | 48 |
| Issue | 1 | Pages | 91-106.e6 |
| PubMed ID | 29343444 | Mgi Jnum | J:272351 |
| Mgi Id | MGI:6284457 | Doi | 10.1016/j.immuni.2017.12.014 |
| Citation | Sharma MD, et al. (2018) Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation into Ly6c(+)CD103(+) Monocytic Antigen-Presenting Cells in Tumors. Immunity 48(1):91-106.e6 |
| abstractText | CD103(+) dendritic cells are critical for cross-presentation of tumor antigens. Here we have shown that during immunotherapy, large numbers of cells expressing CD103 arose in murine tumors via direct differentiation of Ly6c(+) monocytic precursors. These Ly6c(+)CD103(+) cells could derive from bone-marrow monocytic progenitors (cMoPs) or from peripheral cells present within the myeloid-derived suppressor cell (MDSC) population. Differentiation was controlled by inflammation-induced activation of the transcription factor p53, which drove upregulation of Batf3 and acquisition of the Ly6c(+)CD103(+) phenotype. Mice with a targeted deletion of p53 in myeloid cells selectively lost the Ly6c(+)CD103(+) population and became unable to respond to multiple forms of immunotherapy and immunogenic chemotherapy. Conversely, increasing p53 expression using a p53-agonist drug caused a sustained increase in Ly6c(+)CD103(+) cells in tumors during immunotherapy, which markedly enhanced the efficacy and duration of response. Thus, p53-driven differentiation of Ly6c(+)CD103(+) monocytic cells represents a potent and previously unrecognized target for immunotherapy. |
