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.

TAM 受体属于受体酪氨酸激酶家族，由 Tyro3、Axl 和 Mertk 受体 (TAM) 组成，是高等真核生物炎症的重要稳态调节剂。TAM 与其配体 Gas6 和 ProteinS 一起充当磷脂酰丝氨酸 (PtdSer) 的受体，这是一种阴离子磷脂，可在凋亡和应激细胞表面外化。TAM 受体，特别是 Mertk，已被证实在胞吞作用过程中发挥作用，吞噬死亡细胞。除了是 efferocytic 受体，TAM 还是多效性免疫调节剂，因为在各种小鼠模型中缺乏 TAM 受体会导致慢性炎症和自身免疫。由于它们的免疫调节作用，PtdSer-TAM 受体信号轴已被很好地表征为全局免疫抑制信号，在癌症中，新兴文献表明 TAM 受体与癌症免疫学和抗肿瘤治疗有关。在肿瘤微环境中，免疫抑制信号，例如源自 TAM 受体信号的信号，可能不利于抗肿瘤治疗。在本章中，我们将讨论 TAM 受体在肿瘤微环境中的免疫调节功能，以及差异表达的 TAM 受体的作用及其与免疫细胞和肿瘤细胞的相互作用。最后，我们描述了当前用于靶向多种癌症中的 TAM 的策略及其在免疫治疗中的意义。例如源自 TAM 受体信号的那些可能不利于抗肿瘤治疗。在本章中，我们将讨论 TAM 受体在肿瘤微环境中的免疫调节功能，以及差异表达的 TAM 受体的作用及其与免疫细胞和肿瘤细胞的相互作用。最后，我们描述了当前用于靶向多种癌症中的 TAM 的策略及其在免疫治疗中的意义。例如源自 TAM 受体信号的那些可能不利于抗肿瘤治疗。在本章中，我们将讨论 TAM 受体在肿瘤微环境中的免疫调节功能，以及差异表达的 TAM 受体的作用及其与免疫细胞和肿瘤细胞的相互作用。最后，我们描述了当前用于靶向多种癌症中的 TAM 的策略及其在免疫治疗中的意义。