Role of NPRA in MDSC mediated suppression in cancer (P2071)

Abstract

Abstract It is now evident that inadequate function of the host immune system is due to suppressive factors such as myeloid derived suppressor cells (MDSC). In our study we found that MDSCs isolated from tumor bearing mice expressed high levels of natriuretic peptide receptor A (NPRA) a receptor for atrial natriuretic peptide (ANP). Since MDSCs play a pivotal role in tumorigenesis, we addressed whether NPRA signaling may be linked with altered differentiation of myeloid cells and their suppressive function. We examined the wild type and NPRA deficient mice for MDSC differentiation, and the results showed that NPRA deficient mice exhibited restricted tumor growth and altered differentiation of MDSCs. Next we investigated the link between ANP levels and accumulation of MDSCs. Increase in ANP levels triggered expansion of MDSC. MDSCs suppressed T cells via reactive oxygen species (ROS), and increase in NPRA expression was associated with decreased miR150 as well as increased expression of Nox. NPRA KO mice showed increased expression of miR150 compared to WT mice.Our experiments suggested that activation of NPRA and was regulated by a key micro RNA, miR-150. Taken together, these results suggest a key role to NPRA signaling in myeloid cell differentiation and cancer progression.