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TAM Receptor Inhibition-Implications for Cancer and the Immune System

Pia Aehnlich1, Richard Morgan Powell1, Marlies J W Peeters1

  • 1National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital Herlev, 2730 Herlev, Denmark.

Cancers
|April 3, 2021
PubMed

Insights

Tyro3, Axl, and MerTK (TAM) receptors regulate immune responses and efferocytosis. Inhibiting TAM signaling in cancer offers therapeutic potential but may harm anti-cancer immunity due to opposing roles in innate and T cells.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Tyro3, Axl, and MerTK (TAM) receptors are tyrosine kinases crucial for efferocytosis and immune balance.
  • TAM receptors bind ligands like Gas6 and Pros1, facilitating the clearance of apoptotic cells and suppressing inflammation in innate cells.
  • MerTK signaling in T cells is costimulatory, promoting T cell activation and function.

Purpose of the Study:

  • To review the dual role of TAM receptor signaling in cancer and immunity.
  • To discuss the therapeutic potential and immunological risks of inhibiting TAM signaling in cancer treatment.
  • To examine the complex interactions between cancer cells, immune cells, and TAM signaling within the tumor microenvironment.

Main Methods:

  • Literature review of studies on TAM receptor function in cancer and immunology.
  • Analysis of the effects of TAM inhibition on cancer cells and various immune cell populations.
  • Examination of the interplay between cancer and immune cells in the tumor microenvironment.

Main Results:

  • TAM receptors are aberrantly expressed in various cancers, contributing to oncogenic signaling.
  • Inhibition of TAM signaling can suppress tumor growth in preclinical models.
  • Conversely, TAM inhibition may impair anti-cancer immune responses due to their roles in T cell activation.

Conclusions:

  • TAM receptors present a therapeutic target in oncology, but their inhibition requires careful consideration of immune consequences.
  • Understanding the context-dependent roles of TAM signaling is critical for developing effective cancer immunotherapies.
  • Balancing the anti-tumor effects with the potential immunosuppression is key for successful therapeutic strategies targeting TAM receptors.
Keywords:
AxlMerTKPD-1TAM receptorscancersmall molecule inhibitors

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