TRAIL: a multifunctional cytokine

Uta Schaefer1, Oksana Voloshanenko, Daniela Willen

  • 1Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany.

Insights

Tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL) shows anti-tumor potential. Understanding the TRAIL/TRAIL-R system in mice is crucial for assessing TRAIL-based cancer therapy safety and efficacy.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • The Tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL) pathway is a key regulator of apoptosis.
  • TRAIL exhibits specific anti-tumor activity with minimal toxicity, making it a promising cancer therapeutic.
  • The TRAIL receptor system differs between humans and mice, necessitating studies in murine models.

Purpose of the Study:

  • To review the physiological role of the TRAIL/TRAIL-R system.
  • To assess the safety and potential side effects of TRAIL-based cancer therapy.
  • To explore the role of TRAIL in immune homeostasis, infection, autoimmune diseases, and tumorigenesis.

Main Methods:

  • Phenotypic analysis of mice deficient in TRAIL or its murine receptor, TRAIL-R (MK/mDR5).
  • Review of recent studies investigating the TRAIL/TRAIL-R system's functions.
  • Analysis of clinical trial data for TRAIL and TRAIL receptor agonists.

Main Results:

  • Studies in TRAIL- and TRAIL-R-deficient mice provide insights into the system's physiological roles.
  • The TRAIL/TRAIL-R system influences immune homeostasis, infection susceptibility, and autoimmune disease development.
  • The role of TRAIL in tumorigenesis remains controversial, requiring further investigation.

Conclusions:

  • Understanding the TRAIL/TRAIL-R system is essential for developing safe and effective TRAIL-based cancer therapies.
  • Further research and clinical trials are needed to optimize TRAIL-R agonists for cancer treatment.
  • TRAIL-based therapies hold promise, potentially in combination with other anti-cancer agents.

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