Immunological role of TAM receptors in the cancer microenvironment

TAM receptors belong to the family of receptor tyrosine kinases, comprising of Tyro3, Axl and Mertk receptors (TAMs) and are important homeostatic regulators of inflammation in higher eukaryotes. Along with their ligands, Gas6 and ProteinS, TAMs acts as receptors to phosphatidylserine (PtdSer), an anionic phospholipid that becomes externalized on the surface of apoptotic and stressed cells. TAM receptors, specially Mertk, have been well established to play a role in the process of efferocytosis, the engulfment of dying cells. Besides being efferocytic receptors, TAMs are pleiotropic immune modulators as the lack of TAM receptors in various mouse models lead to chronic inflammation and autoimmunity. Owing to their immune modulatory role, the PtdSer-TAM receptor signaling axis has been well characterized as a global immune-suppressive signal, and in cancers, and emerging literature implicates TAM receptors in cancer immunology and anti-tumor therapeutics. In the tumor microenvironment, immune-suppressive signals, such as ones that originate from TAM receptor signaling can be detrimental to anti-tumor therapy. In this chapter, we discuss immune modulatory functions of TAM receptors in the tumor microenvironment as well role of differentially expressed TAM receptors and their interactions with immune and tumor cells. Finally, we describe current strategies being utilized for targeting TAMs in several cancers and their implications in immunotherapy.