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RESEARCH PRODUCT
RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis
Mario P. ColomboSilvia TartariLaura StraussFrancesca Maria ConsonniFrancesco ZitelliSabina SangalettiClaudio TripodoAchille AnselmoChiara PortaGábor J. SzebeniSara MorlacchiMaria Grazia TotaroAndrea DoniAntonio SicaAntonio Sicasubject
MaleCancer ResearchMyeloidNeutrophilsMacrophageCellular differentiationApoptosisMonocyteMonocyteshemic and lymphatic diseasesMyeloid CellsSOCS3Myeloid CellMyelopoiesisMice KnockoutMicroscopy ConfocalReverse Transcriptase Polymerase Chain ReactionMedicine (all)NeutrophilCell DifferentiationNuclear Receptor Subfamily 1 Group F Member 3Animals; Apoptosis; Cell Differentiation; Cell Line Tumor; Cytokines; Female; Gene Expression Regulation Neoplastic; Granulocytes; Humans; Immunohistochemistry; Macrophages; Male; Mice 129 Strain; Mice Inbred C57BL; Mice Knockout; Microscopy Confocal; Monocytes; Myeloid Cells; Myelopoiesis; Neoplasms Experimental; Neutrophils; Nuclear Receptor Subfamily 1 Group F Member 3; Reverse Transcriptase Polymerase Chain Reaction; Tumor Burden; Cancer Research; Cell Biology; Oncology; Medicine (all)ImmunohistochemistryTumor BurdenGene Expression Regulation NeoplasticHaematopoiesismedicine.anatomical_structureOncologyCytokinesFemaleMyelopoiesisHumanMice 129 StrainBiologySettore MED/08 - Anatomia PatologicaGranulopoiesisArticleMyelopoiesiCell Line TumormedicineAnimalsHumansCytokineInnate immune systemAnimalMacrophagesApoptosiGranulocyteNeoplasms ExperimentalCell BiologyMice Inbred C57BLImmunologyCancer researchIRF8Granulocytesdescription
Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We identified subsets of MDSCs and TAMs based on the expression of retinoic-acid-related orphan receptor (RORC1/RORγ) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBPβ) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.1). RORC1 supported tumor-promoting innate immunity by protecting MDSCs from apoptosis, mediating TAM differentiation and M2 polarization, and limiting tumor infiltration by mature neutrophils. Accordingly, ablation of RORC1 in the hematopoietic compartment prevented cancer-driven myelopoiesis, resulting in inhibition of tumor growth and metastasis. Strauss et al. show that RORC1 orchestrates myelopoiesis and supports tumor-promoting innate immunity. Importantly, ablation of RORC1 in the myeloid compartment inhibits tumor growth and metastasis, suggesting a cancer therapeutic approach.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-08-01 |