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Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34(+) progenitor cell-derived NK cells
Umbilical cord blood (UCB) CD34(+) progenitor cell-derived natural killer (NK) cells exert efficient cytotoxicity against various melanoma cell lines. Of interest, the relative cytotoxic performance of individual UCB donors was consistent throughout the melanoma panel and correlated with IFNγ, TNF,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329179/ https://www.ncbi.nlm.nih.gov/pubmed/37426355 http://dx.doi.org/10.1016/j.isci.2023.107078 |
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author | van Vliet, Amanda A. Peters, Ella Vodegel, Denise Steenmans, Daniëlle Raimo, Monica Gibbs, Susan de Gruijl, Tanja D. Duru, Adil D. Spanholtz, Jan Georgoudaki, Anna-Maria |
author_facet | van Vliet, Amanda A. Peters, Ella Vodegel, Denise Steenmans, Daniëlle Raimo, Monica Gibbs, Susan de Gruijl, Tanja D. Duru, Adil D. Spanholtz, Jan Georgoudaki, Anna-Maria |
author_sort | van Vliet, Amanda A. |
collection | PubMed |
description | Umbilical cord blood (UCB) CD34(+) progenitor cell-derived natural killer (NK) cells exert efficient cytotoxicity against various melanoma cell lines. Of interest, the relative cytotoxic performance of individual UCB donors was consistent throughout the melanoma panel and correlated with IFNγ, TNF, perforin and granzyme B levels. Importantly, intrinsic perforin and Granzyme B load predicts NK cell cytotoxic capacity. Exploring the mode of action revealed involvement of the activating receptors NKG2D, DNAM-1, NKp30, NKp44, NKp46 and most importantly of TRAIL. Strikingly, combinatorial receptor blocking led to more pronounced inhibition of cytotoxicity (up to 95%) than individual receptor blocking, especially in combination with TRAIL-blocking, suggesting synergistic cytotoxic NK cell activity via engagement of multiple receptors which was also confirmed in a spheroid model. Importantly, lack of NK cell-related gene signature in metastatic melanomas correlates with poor survival highlighting the clinical significance of NK cell therapies as a promising treatment for high-risk melanoma patients. |
format | Online Article Text |
id | pubmed-10329179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103291792023-07-09 Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34(+) progenitor cell-derived NK cells van Vliet, Amanda A. Peters, Ella Vodegel, Denise Steenmans, Daniëlle Raimo, Monica Gibbs, Susan de Gruijl, Tanja D. Duru, Adil D. Spanholtz, Jan Georgoudaki, Anna-Maria iScience Article Umbilical cord blood (UCB) CD34(+) progenitor cell-derived natural killer (NK) cells exert efficient cytotoxicity against various melanoma cell lines. Of interest, the relative cytotoxic performance of individual UCB donors was consistent throughout the melanoma panel and correlated with IFNγ, TNF, perforin and granzyme B levels. Importantly, intrinsic perforin and Granzyme B load predicts NK cell cytotoxic capacity. Exploring the mode of action revealed involvement of the activating receptors NKG2D, DNAM-1, NKp30, NKp44, NKp46 and most importantly of TRAIL. Strikingly, combinatorial receptor blocking led to more pronounced inhibition of cytotoxicity (up to 95%) than individual receptor blocking, especially in combination with TRAIL-blocking, suggesting synergistic cytotoxic NK cell activity via engagement of multiple receptors which was also confirmed in a spheroid model. Importantly, lack of NK cell-related gene signature in metastatic melanomas correlates with poor survival highlighting the clinical significance of NK cell therapies as a promising treatment for high-risk melanoma patients. Elsevier 2023-06-09 /pmc/articles/PMC10329179/ /pubmed/37426355 http://dx.doi.org/10.1016/j.isci.2023.107078 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article van Vliet, Amanda A. Peters, Ella Vodegel, Denise Steenmans, Daniëlle Raimo, Monica Gibbs, Susan de Gruijl, Tanja D. Duru, Adil D. Spanholtz, Jan Georgoudaki, Anna-Maria Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34(+) progenitor cell-derived NK cells |
title | Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34(+) progenitor cell-derived NK cells |
title_full | Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34(+) progenitor cell-derived NK cells |
title_fullStr | Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34(+) progenitor cell-derived NK cells |
title_full_unstemmed | Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34(+) progenitor cell-derived NK cells |
title_short | Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34(+) progenitor cell-derived NK cells |
title_sort | early trail-engagement elicits potent multimodal targeting of melanoma by cd34(+) progenitor cell-derived nk cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329179/ https://www.ncbi.nlm.nih.gov/pubmed/37426355 http://dx.doi.org/10.1016/j.isci.2023.107078 |
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