TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• TAM receptors (TYRO3, AXL, MERTK) are activated by Protein S (PROS1) or Growth Arrest-Specific 6 (GAS6) binding to apoptotic phosphatidylserine.
• These receptors are vital for efferocytosis by antigen-presenting cells and are expressed throughout the tumor microenvironment.
• TAM receptors function as oncogenes, promoting cancer cell survival and resistance to therapy.

Purpose of the Study:

• To review the multifaceted roles of TAM receptors within the tumor microenvironment.
• To highlight the recently discovered function of MERTK in activated T cells.
• To discuss the implications of TAM receptor activity for anti-tumor immunity and therapeutic strategies.

Main Methods:

• Literature review and synthesis of existing research on TAM receptors.
• Analysis of TAM receptor expression and function in various cancer types.
• Examination of the role of TAM receptors in T cell activation and immune response.

Main Results:

• TAM receptors are expressed by most cells in the tumor microenvironment and are frequently overexpressed in cancers.
• These receptors exhibit both pro-oncogenic and immune-inhibitory functions.
• Emerging evidence shows TAM receptors act as costimulatory molecules on human T cells, particularly MERTK.

Conclusions:

• The complex and often contradictory roles of TAM receptors in cancer necessitate careful consideration for therapeutic targeting.
• Understanding the dual function of TAM receptors in both tumor cells and immune cells is critical for developing effective cancer therapies.
• Targeting TAM receptors, especially MERTK in T cells, holds potential for enhancing anti-tumor immunity.