MiR-142-3p Prevents Macrophage Differentiation during Cancer-Induced Myelopoiesis

Nada Sonda, Francesca Simonato, Elisa Peranzoni, Bianca Calì, Stefania Bortoluzzi, Andrea Bisognin, Ena Wang, Francesco M. Marincola, Luigi Naldini, Bernhard Gentner, Christian Trautwein, Sara Dutton Sackett, Paola Zanovello, Barbara Molon, Vincenzo Bronte

Research output: Contribution to journalArticle

85 Citations (Scopus)

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 theirimmunosuppressive function in tumor. Tumor-released cytokines signaling through gp130, the common subunit of the interleukin-6 cytokine receptor family, induced the LAP*x2217; 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 toits 5' mRNA coding sequence. Enforced miR expression impaired macrophage differentiation both invitro and invivo. Mice constitutively expressing miR-142-3p in the bone marrow showed a marked increase in survival following immunotherapy with tumor-specific T lymphocytes. By modulatinga 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.

Original languageEnglish
Pages (from-to)1236-1249
Number of pages14
JournalImmunity
Volume38
Issue number6
DOIs
Publication statusPublished - 27 Jun 2013
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Sonda, N., Simonato, F., Peranzoni, E., Calì, B., Bortoluzzi, S., Bisognin, A., Wang, E., Marincola, F. M., Naldini, L., Gentner, B., Trautwein, C., Sackett, S. D., Zanovello, P., Molon, B., & Bronte, V. (2013). MiR-142-3p Prevents Macrophage Differentiation during Cancer-Induced Myelopoiesis. Immunity, 38(6), 1236-1249. https://doi.org/10.1016/j.immuni.2013.06.004