A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in mice

Erika Zonari, Ferdinando Pucci, Massimo Saini, Roberta Mazzieri, Letterio S. Politi, Bernhard Gentner, Luigi Naldini

Research output: Contribution to journalArticlepeer-review

Abstract

A productive immune response requires transient upregulation of the microRNA miR-155 in hematopoietic cells mediating innate and adaptive immunity. In order to investigate miR-155 in the context of tumor-associated immune responses, we stably knocked down (KD) miR-155 in the myeloid compartment of MMTV-PyMT mice, a mouse model of spontaneous breast carcinogenesis that closely mimics tumor-host interactions seen in humans. Notably, miR-155/KD significantly accelerated tumor growth by impairing classic activation of tumor-associated macrophages (TAMs). This created an imbalance toward a protumoral microenvironment as evidenced by a lower proportion of CD11c+ TAMs, reduced expression of activation markers, and the skewing of immune cells within the tumor toward an macrophage type 2/T helper 2 response. This study highlights the importance of tumor-infiltrating hematopoietic cells in constraining carcinogenesis and establishes an antitumoral function of a prototypical oncomiR.

Original languageEnglish
Pages (from-to)243-252
Number of pages10
JournalBlood
Volume122
Issue number2
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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