RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis

Laura Strauss, Sabina Sangaletti, Francesca Maria Consonni, Gabor Szebeni, Sara Morlacchi, Maria Grazia Totaro, Chiara Porta, Achille Anselmo, Silvia Tartari, Andrea Doni, Francesco Zitelli, Claudio Tripodo, Mario P. Colombo, Antonio Sica

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)253-269
Number of pages17
JournalCancer Cell
Volume28
Issue number2
DOIs
Publication statusPublished - Aug 10 2015

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology
  • Medicine(all)

Fingerprint Dive into the research topics of 'RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis'. Together they form a unique fingerprint.

  • Cite this

    Strauss, L., Sangaletti, S., Consonni, F. M., Szebeni, G., Morlacchi, S., Totaro, M. G., Porta, C., Anselmo, A., Tartari, S., Doni, A., Zitelli, F., Tripodo, C., Colombo, M. P., & Sica, A. (2015). RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis. Cancer Cell, 28(2), 253-269. https://doi.org/10.1016/j.ccell.2015.07.006