Abstract 3556: MiR-506 suppresses tumor progression by reprogramming macrophage polarization in pancreatic ductal adenocarcinoma

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancy owing to its aggressive nature and tumor-associated macrophages (TAMs) significantly promote disease progression by representing an immunosuppressive phenotype in PDAC. Macrophages could be functionally reprogrammed to opposite phenotype owning to different microenvironment and STAT3 (signal transducer and activator of transcription 3) activation may play an essential role in TAM polarization, directly contributing to local immunosuppression. Our recent study demonstrated that MiR-506 functioned as a tumor suppressor in many cancer types through the regulation of multiple pathways and directly targeted STAT3 in PDAC cells. In this study, we hypothesized that MiR-506 could affect tumor microenvironment and exert a tumor suppressive function in PDAC by reprograming TAM polarization through targeting STAT3 in TAM. Our results provided evidence that MiR-506 downregulation was associated with less immunosuppressive TAMs accumulation and better prognosis in human PDAC. MiR-506 could reduce the infiltration of immunosuppressive TAMs and inhibit the PDAC progression in mouse model. MiR-506 reprogramed macrophage polarization from an immunosuppressive phenotype to immune-activated phenotype through direct targeting the STAT3 axis. Silencing and inhibiting STAT3 recapitulated the effects of MiR-506. These findings expand the known mechanisms of MiR-506-mediated tumor suppression to reprogramming TAM polarization and suggest a strategy for using MiR-506 as an anti-STAT3 approach to PDAC immunotherapy. Citation Format: Longhao Sun, Qianqian Song, Weijun Tian, Zhixiang Zhang. MiR-506 suppresses tumor progression by reprogramming macrophage polarization in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3556.