RORC1 regulates tumor-promoting ″emergency″ granulo-monocytopoiesis

13^th Asia-Pacific Oncologists Annual Meeting

October 17-19, 2016 Kuala Lumpur, Malaysia

Laura Strauss

Universita` del Piemonte Orientale, Italy

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloidderived 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/ROR�³) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBP�³ 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. Thus, inhibition of RORC1-dependent myelopoiesis may represent a therapeutic approach to prevent the induction of the tumor-promoting host macro- and micro-environments.

Biography :

Email: antonio.sica@humanitasresearch.it