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 journalArticle

54 Citations (Scopus)

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 (US)
Pages (from-to)243-252
Number of pages10
JournalBlood
Volume122
Issue number2
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Tumors
Macrophages
Neoplasms
Carcinogenesis
Chemical activation
Adaptive Immunity
MicroRNAs
Innate Immunity
Transient analysis
Breast
Up-Regulation
Biomarkers
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in mice. / Zonari, Erika; Pucci, Ferdinando; Saini, Massimo; Mazzieri, Roberta; Politi, Letterio S.; Gentner, Bernhard; Naldini, Luigi.

In: Blood, Vol. 122, No. 2, 01.01.2013, p. 243-252.

Research output: Contribution to journalArticle

Zonari, Erika ; Pucci, Ferdinando ; Saini, Massimo ; Mazzieri, Roberta ; Politi, Letterio S. ; Gentner, Bernhard ; Naldini, Luigi. / A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in mice. In: Blood. 2013 ; Vol. 122, No. 2. pp. 243-252.
@article{c599221c08f940929474608c5d64b2d5,
title = "A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in mice",
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.",
author = "Erika Zonari and Ferdinando Pucci and Massimo Saini and Roberta Mazzieri and Politi, {Letterio S.} and Bernhard Gentner and Luigi Naldini",
year = "2013",
month = "1",
day = "1",
doi = "10.1182/blood-2012-08-449306",
language = "English (US)",
volume = "122",
pages = "243--252",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in mice

AU - Zonari, Erika

AU - Pucci, Ferdinando

AU - Saini, Massimo

AU - Mazzieri, Roberta

AU - Politi, Letterio S.

AU - Gentner, Bernhard

AU - Naldini, Luigi

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84884478648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884478648&partnerID=8YFLogxK

U2 - 10.1182/blood-2012-08-449306

DO - 10.1182/blood-2012-08-449306

M3 - Article

VL - 122

SP - 243

EP - 252

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -