ROR1C Regulates Differentiation of Myeloid-Derived Suppressor Cells

Abstract

Myeloid-derived suppressor cells (MDSCs) play a major role in cancer. MDSC expansion is closely associated with tumor progression, but molecular mechanisms of this expansion remain poorly understood. In this issue of Cancer Cell, Strauss and colleagues describe the roles of the nuclear receptor ROR1C in the regulation of MDSC differentiation and expansion.

Figure 1. RORC1 Involvement in Myeloid Lineage Differentiation

Brown shows the general pathway of differentiation of neutrophils and mononuclear cells in healthy individuals. Hematopoietic stem cells (HSC) differentiate into common myeloid progenitors (CMP), then into granulocytes macrophage progenitors (GMP), which give rise to mature neutrophils via sequential steps of differentiation involving myeloblasts (MB), promyelocytes (PM), myelocytes (MC), metamyelocytes (MM), and band forms (BF). Differentiation of macrophages (MΦ) and DCs involve macrophage/dendritic cell progenitors (MDP), DC progenitors (CDP), pre-cDCs, as well as several types of monocytes. In cancer (blue), tumor-derived factors regulate various molecular pathways, including upregulation of RORC1, which affect all steps of granulocytic and monocytic cell differentiation. RORC1 promotes the accumulation of immature pathologically activated PMN-MDSC neutrophils for the expense of mature PMN. M-MDSCs differentiate to TAM in the tumor site. RORC1 promotes polarization toward the M2 phenotype of TAM.