Susceptibility of melanoma cells to targeted therapy correlates with protection by blood neutrophils
Elevated levels of peripheral blood and tumor tissue neutrophils are associated with poorer clinical response and therapy resistance in melanoma. The underlying mechanism and the role of neutrophils in targeted therapy is still not fully understood. Serum samples of patients with advanced melanoma w...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2 May 2024
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| In: |
Cancers
Year: 2024, Jahrgang: 16, Heft: 9, Pages: 1-28 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers16091767 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/cancers16091767 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2072-6694/16/9/1767 |
| Verfasserangaben: | Simone Wendlinger, Jonas Wohlfarth, Claudia Siedel, Sophia Kreft, Teresa Kilian, Sarah Junker, Luisa Schmid, Tobias Sinnberg, Ulrich Dischinger, Markus V. Heppt, Kilian Wistuba-Hamprecht, Friedegund Meier, Luise Erpenbeck, Elsa Neubert, Matthias Goebeler, Anja Gesierich, David Schrama, Corinna Kosnopfel and Bastian Schilling |
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| 245 | 1 | 0 | |a Susceptibility of melanoma cells to targeted therapy correlates with protection by blood neutrophils |c Simone Wendlinger, Jonas Wohlfarth, Claudia Siedel, Sophia Kreft, Teresa Kilian, Sarah Junker, Luisa Schmid, Tobias Sinnberg, Ulrich Dischinger, Markus V. Heppt, Kilian Wistuba-Hamprecht, Friedegund Meier, Luise Erpenbeck, Elsa Neubert, Matthias Goebeler, Anja Gesierich, David Schrama, Corinna Kosnopfel and Bastian Schilling |
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| 520 | |a Elevated levels of peripheral blood and tumor tissue neutrophils are associated with poorer clinical response and therapy resistance in melanoma. The underlying mechanism and the role of neutrophils in targeted therapy is still not fully understood. Serum samples of patients with advanced melanoma were collected and neutrophil-associated serum markers were measured and correlated with response to targeted therapy. Blood neutrophils from healthy donors and patients with advanced melanoma were isolated, and their phenotypes, as well as their in vitro functions, were compared. In vitro functional tests were conducted through nonadherent cocultures with melanoma cells. Protection of melanoma cell lines by neutrophils was assessed under MAPK inhibition. Blood neutrophils from advanced melanoma patients exhibited lower CD16 expression compared to healthy donors. In vitro, both healthy-donor- and patient-derived neutrophils prevented melanoma cell apoptosis upon dual MAPK inhibition. The effect depended on cell-cell contact and melanoma cell susceptibility to treatment. Interference with protease activity of neutrophils prevented melanoma cell protection during treatment in cocultures. The negative correlation between neutrophils and melanoma outcomes seems to be linked to a protumoral function of neutrophils. In vitro, neutrophils exert a direct protective effect on melanoma cells during dual MAPK inhibition. This study further hints at a crucial role of neutrophil-related protease activity in protection. | ||
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