P3 Macrophage activation in the ovarian cancer tumor microenvironment and design of a novel immunotherapy

Macrophages (Mȹ) perform different roles in the ovarian cancer (OvCa) tumor microenvironment (TME): pro-inflammatory M1 Mȹ drive anti-tumor immune response; and pro-tumoral, anti-phagocytic M2-like Mȹ promote OvCa tumorigenicity. SIRPα, a Mȹ surface receptor, is known to prevent phagocytic activity of Mȹ upon binding with CD47 on OvCa cells. OvCa triggers the expression of other surface proteins on macrophages, that continue to suppress Mȹ based immunity, thereby promoting platinum resistance and disease progression. We assess profiles of immuno-regulatory proteins SIRPα, CD47, and macrophage-associated protease MMP-9, as well as M1 and M2 Mȹ surface markers, CD68 and CD163. This profile of Mȹ activity in the OvCa TME were investigated using clinical tumor microarrays (TMA) and 3 dimensional (3D) cell culture OvCa organoid models. By understanding the basis of immune suppression specific to the OvCa TME, we also design a novel nanomedicine-based immunotherapy for OvCa.