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Stem Cell Regulation by Death Ligands and Their Use in Cell Therapy

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TRAIL, Fas Ligand, TNF and TLR3 in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 12))

Abstract

Stem cells are an essential to repair damaged tissues. Their functions, proliferation and differentiation need to be tightly controlled, as impairments can lead to various diseases including cancer. Induction of apoptosis is one way to control the number of stem cells and to eliminate rogue and/or precancerous cells. One way of triggering apoptosis, and probably the physiologically most important one, is via binding of death ligand to their cognate receptors. The death receptor–ligand family encompasses five pairs: FAS/FASL; TNF-R1/TNF; DR3/TL1A and TWEAK; DR4 and DR5/TRAIL; and DR6/unknown ligand. Of these, FASL and TRAIL and to a lesser extent TNF are strong inducers of apoptosis, whereas the others possess relative weak cell-death-inducing activity. Interestingly, these death receptors and ligands also have non-canonical functions and in specific cellular and molecular contexts can regulate cell proliferation, differentiation, chemokine production and inflammatory responses. Some of these non-apoptotic functions have been shown to be of relevance in stem and progenitor cells.

Stem cells have also been used as part of cell therapies in connection with delivery of death ligands to target their respective receptors, in particular in experimental anti-cancer therapies. Stem cells, at least some types, are attractive in these approaches because they are capable to infiltrate certain tissues including tumours to deliver their therapeutic payload. This way of cellular delivery can be more efficacious and specific compared to recombinant proteins or direct gene therapy.

This chapter summarises our current understanding of stem cell regulation by death receptor–ligand signalling and in the second part how certain types of stem cells have been used to deliver death-ligand gene therapies in the laboratory and increasingly in clinical trials.

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    Andrea Mohr & Ralf Zwacka

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Mohr, A., Zwacka, R. (2017). Stem Cell Regulation by Death Ligands and Their Use in Cell Therapy. In: Micheau, O. (eds) TRAIL, Fas Ligand, TNF and TLR3 in Cancer. Resistance to Targeted Anti-Cancer Therapeutics, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-56805-8_6

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