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Tracking death dealing by Fas and TRAIL in lymphatic neoplastic disorders: pathways, targets, and therapeutic tools
Richard Greil1, Gabriele Anether, Karin Johrer
1Department of Internal Medicine, University of Innsbruck Medical School, Austria. richard.greil@uibk.ac.at
Abstract:
In the past decade, it was concluded from a number of investigations that death domain-containing members of the tumor necrosis factor-receptor (TNF-R) family and their ligands such as Fas/FasL and TNF-related apoptosis-inducing ligand (TRAIL)-R/TRAIL are essential for maintaining an intact immune system for surveillance against infection and cancer development and that nondeath domain-containing members such as CD30 or CD40 are involved in the fine tuning of this system during the selection process of the lymphatic system. In line with this conclusion are the observations that alterations in structure, function, and regulation of these molecules contribute to autoimmunity and cancer development of the lymphoid system. Besides controlling size and function of the lymphoid cell pool, Fas/FasL and TRAIL-R/TRAIL regulate myelopoiesis and the dendritic cell functions, and severe alterations of these lineages during the outgrowth and expansion of the lymphoid tumors have been reported. It is the aim of this review to summarize what is currently known about the complex role of these two death receptor/ligand systems in normal, disturbed, and neoplastic hemato-/lymphopoiesis and to point out how such knowledge can be used in developing novel, therapeutic options and the problems that will have to be faced along the way.
Insights
Tumor necrosis factor receptor (TNF-R) family members, Fas/FasL and TRAIL-R/TRAIL, are crucial for immune surveillance and lymphoid system regulation. Dysregulation contributes to autoimmunity and lymphoid cancers, offering therapeutic targets.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Death domain-containing TNF-R family members (e.g., Fas/FasL, TRAIL-R/TRAIL) are vital for immune system integrity.
- Non-death domain members (e.g., CD30, CD40) fine-tune lymphatic system selection.
- Alterations in these molecules are linked to autoimmunity and lymphoid cancers.
Purpose of the Study:
- To review the multifaceted roles of Fas/FasL and TRAIL-R/TRAIL systems in hematopoiesis and lymphopoiesis.
- To explore their involvement in normal, aberrant, and neoplastic conditions.
- To identify potential therapeutic strategies and challenges based on current knowledge.
Main Methods:
- Literature review of investigations on TNF-R family members.
- Analysis of molecular mechanisms in immune regulation and lymphoid development.
- Synthesis of data on disease associations and therapeutic implications.
Main Results:
- Fas/FasL and TRAIL-R/TRAIL are essential for immune surveillance against infection and cancer.
- These systems regulate myelopoiesis and dendritic cell functions.
- Severe alterations in these lineages are observed during lymphoid tumor progression.
Conclusions:
- The complex roles of Fas/FasL and TRAIL-R/TRAIL in hemato-/lymphopoiesis are critical.
- Understanding these systems can lead to novel therapeutic approaches for lymphoid malignancies.
- Challenges exist in translating this knowledge into effective treatments.
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