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


Journal

Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732

Informations de publication

Date de publication:
Feb 2020
Historique:
received: 08 07 2019
accepted: 18 10 2019
pubmed: 31 10 2019
medline: 15 2 2020
entrez: 31 10 2019
Statut: ppublish

Résumé

The TAM receptors-TYRO3, AXL, MERTK-are pleiotropically expressed receptors in both healthy and diseased tissue. A complex of the ligands Protein S (PROS1) or Growth Arrest-Specific 6 (GAS6) with apoptotic phosphatidylserine activates the TAM receptors. Hence, this receptor family is essential for the efferocytosis of apoptotic material by antigen-presenting cells. In addition, TAM receptors are expressed by virtually all cells of the tumor microenvironment. They are also potent oncogenes, frequently overexpressed in cancer and involved in survival and therapy resistance. Due to their pro-oncogenic and immune-inhibitory traits, TAM receptors have emerged as promising targets for cancer therapy. Recently, TAM receptors have been described to function as costimulatory molecules on human T cells. TAM receptors' ambivalent functions on many different cell types therefore make therapeutic targeting not straight-forward. In this review we summarize our current knowledge of the function of TAM receptors in the tumor microenvironment. We place particular focus on TAM receptors and the recently unraveled role of MERTK in activated T cells and potential consequences for anti-tumor immunity.

Identifiants

pubmed: 31664482
doi: 10.1007/s00262-019-02421-w
pii: 10.1007/s00262-019-02421-w
pmc: PMC7000491
doi:

Substances chimiques

Antineoplastic Agents 0
Biomarkers 0
Proto-Oncogene Proteins 0
MERTK protein, human EC 2.7.10.1
Receptor Protein-Tyrosine Kinases EC 2.7.10.1
TYRO3 protein, human EC 2.7.10.1
c-Mer Tyrosine Kinase EC 2.7.10.1
Axl Receptor Tyrosine Kinase 0
AXL protein, human 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

237-244

Subventions

Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 641549
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 641549

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Auteurs

Marlies J W Peeters (MJW)

National Center for Cancer Immune Therapy, Department of Oncology, University Hospital Herlev, Borgmester Ib Juuls Vej 25C, Copenhagen, Denmark. marlies.peeters@regionh.dk.

Anne Rahbech (A)

National Center for Cancer Immune Therapy, Department of Oncology, University Hospital Herlev, Borgmester Ib Juuls Vej 25C, Copenhagen, Denmark.

Per Thor Straten (P)

National Center for Cancer Immune Therapy, Department of Oncology, University Hospital Herlev, Borgmester Ib Juuls Vej 25C, Copenhagen, Denmark.
Inflammation and Cancer Group, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

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Classifications MeSH