IMR Press / FBL / Volume 12 / Issue 10 / DOI: 10.2741/2354

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

TRAIL: a multifunctional cytokine
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1 Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany
Front. Biosci. (Landmark Ed) 2007, 12(10), 3813–3824;
Published: 1 May 2007

The Tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand, TRAIL, has gained much attention due to its specific anti-tumor potential without toxic side effects. TRAIL binds to a complex receptor system. In humans there are two death-inducing receptors for TRAIL while only one is present in mice. The signaling induced by these receptors leads to apoptosis but might also result in activation of survival signals. To assess the safety and possible side effects of TRAIL-based cancer therapy it is necessary to understand the physiological role of the TRAIL/TRAIL-R system. This has been addressed in mice deficient either for TRAIL or for its only murine apoptosis-inducing receptor, TRAIL-R (MK/mDR5). In this review we will discuss their phenotypes and the results of recent studies on the role of TRAIL in the homeostasis of the immune system, the influence of the TRAIL/TRAIL-R system on infection and autoimmune diseases and the still controversial role of TRAIL in tumorigenesis. Clinical trials with TRAIL and other TRAIL receptor agonists are now under way. It will be exciting to determine which TRAIL-R agonists, either alone or in combination with other anti-cancer therapeutics, will result in better outcome of cancer treatment in the future.

death receptor
NK cells
clinical development
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