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Immunity. 2013 Jun 27;38(6):1236-49. doi: 10.1016/j.immuni.2013.06.004.

miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.

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1
Department of Surgery, Oncology and Gastroenterology, Oncology and Immunology Section, University of Padua, 35128 Padua, Italy.

Abstract

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/EBPβ transcription factor, promoting macrophage generation. miR-142-3p downregulated gp130 by canonical binding to its messenger RNA (mRNA) 3' UTR and repressed C/EBPβ 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.

PMID:
23809164
DOI:
10.1016/j.immuni.2013.06.004
[Indexed for MEDLINE]
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