Susceptibility of Melanoma Cells to Targeted Therapy Correlates with Protection by Blood Neutrophils.

Autor: Wendlinger S; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany.; Mildred Scheel Early Career Center Wuerzburg, University Hospital Wuerzburg, 97080 Würzburg, Germany., Wohlfarth J; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany., Siedel C; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany., Kreft S; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany.; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK., Kilian T; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany., Junker S; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany., Schmid L; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany., Sinnberg T; Division of Dermatooncology, Department of Dermatology, University of Tübingen, 72076 Tübingen, Germany.; Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany., Dischinger U; Department of Endocrinology and Diabetology, University Hospital Würzburg, 97080 Würzburg, Germany., Heppt MV; Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany., Wistuba-Hamprecht K; Skin Cancer Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany., Meier F; Department of Dermatology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.; Skin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases, 01307 Dresden, Germany., Erpenbeck L; Department of Dermatology, University of Münster, 48149 Münster, Germany., Neubert E; Leiden Academic Centre for Drug Research, Leiden University, 2333 Leiden, The Netherlands.; Department of Dermatology, Venereology and Allergology, University Medical Center, Göttingen University, 37075 Göttingen, Germany., Goebeler M; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany., Gesierich A; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany., Schrama D; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany., Kosnopfel C; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany.; Mildred Scheel Early Career Center Wuerzburg, University Hospital Wuerzburg, 97080 Würzburg, Germany.; Department of Hematology, Oncology and Pneumology, University Hospital Münster, 48149 Münster, Germany., Schilling B; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 May 02; Vol. 16 (9). Date of Electronic Publication: 2024 May 02.
DOI: 10.3390/cancers16091767
Abstrakt: 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.
Databáze: MEDLINE
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