| First Author | Sonda N | Year | 2013 |
| Journal | Immunity | Volume | 38 |
| Issue | 6 | Pages | 1236-49 |
| PubMed ID | 23809164 | Mgi Jnum | J:207573 |
| Mgi Id | MGI:5559130 | Doi | 10.1016/j.immuni.2013.06.004 |
| Citation | Sonda N, et al. (2013) miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis. Immunity 38(6):1236-49 |
| abstractText | Tumor progression is accompanied by an altered myelopoiesis causing the accumulation of immunosuppressive cells. Here, we showed that miR-142-3p downregulation promoted macrophage differentiation and determined the acquisition of their immunosuppressive function in tumor. Tumor-released cytokines signaling through gp130, the common subunit of the interleukin-6 cytokine receptor family, induced the LAP * isoform of C/EBPbeta transcription factor, promoting macrophage generation. miR-142-3p downregulated gp130 by canonical binding to its messenger RNA (mRNA) 3' UTR and repressed C/EBPbeta LAP * by noncanonical binding to its 5' mRNA coding sequence. Enforced miR expression impaired macrophage differentiation both in vitro and in vivo. Mice constitutively expressing miR-142-3p in the bone marrow showed a marked increase in survival following immunotherapy with tumor-specific T lymphocytes. By modulating a specific miR in bone marrow precursors, we thus demonstrated the feasibility of altering tumor-induced macrophage differentiation as a potent tool to improve the efficacy of cancer immunotherapy. |
