Activation of a productive immune response requires transient upregulation of miR155 in the hematopoietic compartment. 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 (PyMT), a mouse model of spontaneous breast carcinogenesis that closely mimics tumor-host interactions seen in humans. Notably, myeloid cell specific miR-155 KD significantly accelerated tumor growth, as reflected by increased tumor mass and more pronounced secondary hematopoietic changes, i.e. leukocytosis and anemia. Mechanistically, miR155 KD reduces classical activation of tumor macrophages creating an imbalance towards a protumoral microenvironment as evidenced by up-regulation of the Th2 gene "IL13" in CD4+ T cells. Our studies are one of the first to implicate a miRNA in modulating myeloid responses in the tumor microenvironment. This study further highlights the importance of tumor infiltrating hematopoietic cells in fighting cancer development and establishes an antitumoral function of a prototypical oncomir, underscoring the context-specificity of miRNA regulation.

(2012). Tumor infiltrating myeloid cells: modulators of tumor microenvironment and novel therapeutic targets. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2012).

Tumor infiltrating myeloid cells: modulators of tumor microenvironment and novel therapeutic targets

ZONARI, ERIKA
2012-03-26

Abstract

Activation of a productive immune response requires transient upregulation of miR155 in the hematopoietic compartment. 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 (PyMT), a mouse model of spontaneous breast carcinogenesis that closely mimics tumor-host interactions seen in humans. Notably, myeloid cell specific miR-155 KD significantly accelerated tumor growth, as reflected by increased tumor mass and more pronounced secondary hematopoietic changes, i.e. leukocytosis and anemia. Mechanistically, miR155 KD reduces classical activation of tumor macrophages creating an imbalance towards a protumoral microenvironment as evidenced by up-regulation of the Th2 gene "IL13" in CD4+ T cells. Our studies are one of the first to implicate a miRNA in modulating myeloid responses in the tumor microenvironment. This study further highlights the importance of tumor infiltrating hematopoietic cells in fighting cancer development and establishes an antitumoral function of a prototypical oncomir, underscoring the context-specificity of miRNA regulation.
FERRARI, GIULIANA
NALDINI, LUIGI
TAM, miR-155, tumor microenvironment
BIO/11 - BIOLOGIA MOLECOLARE
English
Scuola di Dottorato in Medicina Traslazionale e Molecolare
MEDICINA TRASLAZIONALE E MOLECOLARE (DIMET) - 45R
23
2009/2010
(2012). Tumor infiltrating myeloid cells: modulators of tumor microenvironment and novel therapeutic targets. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2012).
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/29814
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