Role of tumor-derived exosomal miRNAs in M2-macrophage reprogramming during colorectal cancer progression

Abstract

Colorectal cancer is one of the leading causes of death worldwide. Its incidence and mortality have significantly increased during the past few years. Colorectal cancer cells cross-talk with other cells through exosomes in their tumor microenvironment. One of the ways of cross-talk is through exosomes. Exosomes play a significant role in facilitating cross talk between macrophages and colorectal cancer cells. In this study, exosomes produced by colorectal cancer cells were separated and their impact on the polarization of macrophages was determined. This revealed that early on, these exosomes responsible for pro-inflammatory macrophages, and later, anti-inflammatory macrophages. Anti-inflammatory macrophages are in charge of tumor growth, metastasis, and angiogenesis. Furthermore, CRC exosomes are responsible for increased expression of Programmed death ligand-1, which results in immunosuppression; thus, to inhibit exosomal mediated PD-L1 expression, a small inhibitor that blocks the PD-L1 interaction with PD-1 was discovered.