Tyro3, Axl, Mertk receptor-mediated efferocytosis and immune regulation in the tumor environment

Abstract

Three structurally related tyrosine receptor cell surface kinases, Tyro3, Axl, and Mertk (TAM) have been recognized to modulate immune function, tissue homeostasis, cardiovasculature, and cancer. The TAM receptor family appears to operate in adult mammals across multiple cell types, suggesting both widespread and specific regulation of cell functions and immune niches. TAM family members regulate tissue homeostasis by monitoring the presence of phosphatidylserine expressed on stressed or apoptotic cells. The detection of phosphatidylserine on apoptotic cells requires intermediary molecules that opsonize the dying cells and tether them to TAM receptors on phagocytes. This complex promotes the engulfment of apoptotic cells, also known as efferocytosis, that leads to the resolution of inflammation and tissue healing. The immune mechanisms dictating these processes appear to fall upon specific family members or may involve a complex of different receptors acting cooperatively to resolve and repair damaged tissues. Here, we focus on the role of TAM receptors in triggering efferocytosis and its consequences in the regulation of immune responses in the context of inflammation and cancer.

Keywords: Apoptotic cells; Cancer; Dendritic cells; Macrophages; Receptor tyrosine kinases; Signal transduction; T cells.