TNF Family Members in Immunology, Virology and Cancer Therapy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 4369

Special Issue Editor


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Guest Editor
Universite Bourgogne Franche-Comte, Besancon, France
Interests: TNF receptor members; cross-talks between TNF receptors such as Fas and conventional chemotherapeutic drugs; molecular mechanisms underlying TNFR1 pleiotropic signaling; TRAIL signal transduction

Special Issue Information

Dear Colleagues,

TNF family members display pleiotropic functions. While most of them play a critical role in the immune system, like TNF, only a restricted number are naturally involved and necessary to remove unwanted cells infected by viruses or undergoing transformation. Amongst them TNF-Related Apoptosis-Inducing Ligand (TRAIL), whose binding to its cognate agonist receptors, namely TRAIL-R1/DR4 or TRAIL-R2/DR5 triggers cell death in virally-infected or cancer cells. TNF on the other hand is rather associated with pro-inflammatory functions and its ability to trigger cancer cell death is almost inexistent, unless the NF-kB pathway is shut down. Given that TRAIL administration in vivo is safe, contrary to TNF, TRAIL or its derivatives have has attracted major interest in oncology. Notwithstanding, because inhibition of TNF during anti-PD1 or -PDL1 antitumor therapies is emerging as a good opportunity to overcome resistance to cancer-immunotherapies, rational design and targeting of other members of the TNF family may provide as well novel opportunities in anti-cancer therapies or autoimmune diseases. Because recent evidence indicate that TRAIL receptors may in addition trigger non-apoptotic signaling, cell death upon unresolved ER stress regardless of TRAIL, promote stress-induced inflammation or regulate immune cell activity during viral infections, a better understanding of the TRAIL system or the discovery of novel molecules or means to restore TRAIL-induced apoptosis is likely to open novel therapeutic opportunities in oncology, immune and infectious.

This special issue aims at gathering the most recent findings on TNF/TNFR superfamily members in immunology, virology and cancer therapy. Original articles and reviews are welcome.

Dr. Olivier Micheau
Guest Editor

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Keywords

  • TNFSF
  • TNFRSF
  • Cancer
  • autoimmune diseases
  • infectious diseases
  • oncology
  • immunology
  • virology
  • signaling
  • therapy

Published Papers (1 paper)

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Research

18 pages, 3334 KiB  
Article
Marine Actinomycetes-Derived Secondary Metabolites Overcome TRAIL-Resistance via the Intrinsic Pathway through Downregulation of Survivin and XIAP
by Mohammed I. Y. Elmallah, Sheron Cogo, Andrei A. Constantinescu, Selene Elifio-Esposito, Mohammed S. Abdelfattah and Olivier Micheau
Cells 2020, 9(8), 1760; https://doi.org/10.3390/cells9081760 - 22 Jul 2020
Cited by 18 | Viewed by 3705
Abstract
Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis represents the major hurdle to the clinical use of TRAIL or its derivatives. The discovery and development of lead compounds able to sensitize tumor cells to TRAIL-induced cell death is thus [...] Read more.
Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis represents the major hurdle to the clinical use of TRAIL or its derivatives. The discovery and development of lead compounds able to sensitize tumor cells to TRAIL-induced cell death is thus likely to overcome this limitation. We recently reported that marine actinomycetes’ crude extracts could restore TRAIL sensitivity of the MDA-MB-231 resistant triple negative breast cancer cell line. We demonstrate in this study, that purified secondary metabolites originating from distinct marine actinomycetes (sharkquinone (1), resistomycin (2), undecylprodigiosin (3), butylcyclopentylprodigiosin (4), elloxizanone A (5) and B (6), carboxyexfoliazone (7), and exfoliazone (8)), alone, and in a concentration-dependent manner, induce killing in both MDA-MB-231 and HCT116 cell lines. Combined with TRAIL, these compounds displayed additive to synergistic apoptotic activity in the Jurkat, HCT116 and MDA-MB-231 cell lines. Mechanistically, these secondary metabolites induced and enhanced procaspase-10, -8, -9 and -3 activation leading to an increase in PARP and lamin A/C cleavage. Apoptosis induced by these compounds was blocked by the pan-caspase inhibitor QvD, but not by a deficiency in caspase-8, FADD or TRAIL agonist receptors. Activation of the intrinsic pathway, on the other hand, is likely to explain both their ability to trigger cell death and to restore sensitivity to TRAIL, as it was evidenced that these compounds could induce the downregulation of XIAP and survivin. Our data further highlight that compounds derived from marine sources may lead to novel anti-cancer drug discovery. Full article
(This article belongs to the Special Issue TNF Family Members in Immunology, Virology and Cancer Therapy)
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