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Microfluidic Approach to Resolve Simultaneous and Sequential Cytokine Secretion of Individual Polyfunctional Cells
Published on: March 8, 2024
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.
Abstract:
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.
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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