48P Macrophage-derived exosomal microRNAs regulate macrophage-cancer communications

Abstract

Macrophages are a type of phagocyte, which play a critical role in the immune system. They are involved in both innate and adaptive immunity by either removing pathogens or antigen presentation. It has been shown that macrophages are polarized to subgroups with distinct functions, M1 and M2. M1 polarization is characterized by pro-inflammatory and anti-cancer functions, whereas M2 macrophages promote immune suppression and tumor growth. As small noncoding RNAs, miRNAs have been shown to regulate macrophage polarization. In this study, we further investigate that exosomal miRNAs from macrophages play roles in cancer progression. Specifically, we demonstrated that macrophages could modulate cancer immune microenvironment through upregulation and release of miRNAs. To investigate macrophage and cancer communication in a cancer-immune microenvironment, human macrophage differentiation was performed and co-cultured with human melanoma. Homo sapiens small RNA sequencing was performed by exosome purification from co-cultured human macrophages. The whole transcript expression array was executed in co-cultured human melanoma. M1 polarized macrophage has been shown that pro-inflammatory and anti-cancer functions, whereas M2 macrophages promoted tumor growth and migration. According to small RNA sequencing data,differential exosomal miRNA expression profiles depend on macrophage differentiation and these exosomal miRNAs play roles in cancer progression. The whole transcript expression array represents target genes changed by exosomal miRNA. In this report, we demonstrated exosomal miRNA mediated-communication between cancer and macrophages. Interestingly, M1 or M2 macrophage showed differential exosomal miRNA expression profiles. Specifically, we found that let-7i and miR-19a derived from M1 macrophage induces anti-cancer effect. Due to its anti-cancer efficacy, let-7i and miR-19a could be candidates for therapeutics.