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.
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy and Division of Regenerative Medicine, Gene Therapy and Stem Cells, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Zonari
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Pucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Saini
authors.forename: Roberta
authors.initials: R
authors.lastname: Mazzieri
authors.forename: Letterio S
authors.initials: LS
authors.lastname: Politi
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gentner
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D023061:Gene Order; D005822:Genetic Vectors; D007113:Immunity, Innate / Q000235:genetics*; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D051057:Proto-Oncogene Proteins c-akt