2026-06-14T06:44:15Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/76142024-11-29T15:51:32Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Forsthuber, Agnes
author
Lipp, Katharina
author
Andersen, Liisa
author
Ebersberger, Stefanie
author
Graña Castro, Osvaldo
author
Ellmeier, Wilfried
author
Petzelbauer, Peter
author
Lichtenberger, Beate M
author
Loewe, Robert
funder
Fundación Jesús Serra
2019-05-20T10:48:21Z
2019-05-20T10:48:21Z
2019-01
J Invest Dermatol. 2019;139(1):186-194.
10.1016/j.jid.2018.07.006
1523-1747
0022202X
The Journal of investigative dermatology
30009831
http://hdl.handle.net/20.500.12105/7614
Chemokines mold the tumor microenvironment by recruiting distinct immune cell populations, thereby strongly influencing disease progression. Previously, we showed that CXCL5 expression is upregulated in advanced stages of primary melanomas, which correlates with the presence of neutrophils in the tumor. The analysis of neutrophil populations in various tissues revealed a distinct phenotype of tumor-associated neutrophils. Tumor-associated neutrophils expressed PD-L1, CXCR4, CCR5, Adam17, and Nos2 and were immunosuppressive in a T-cell proliferation assay. To investigate the impact of CXCL5 and neutrophils in vivo, we established a syngeneic mouse tumor transplantation model using CXCL5-overexpressing and control melanoma cell lines. Growth behavior or vascularization of primary tumors was not affected by CXCL5 expression and neutrophils alone. However, in combination with Poly(I:C), tumor-associated neutrophils were able to attenuate induced antitumoral T-cell responses. CXCL5-overexpressing tumors had reduced lung metastasis compared with control tumors. Neutrophil depletion reversed this effect. In vitro, unstimulated lung-derived neutrophils had higher levels of reactive oxygen species compared with tumor-associated neutrophils, and CXCL5 stimulation further increased reactive oxygen species levels. In summary, in melanoma, neutrophils play a context-dependent role that is influenced by local or systemic factors, and interfere with therapies activating the acquired immune system. Actively switching neutrophils into antitumorigenic mode might be a new therapeutic strategy.
eng
SUPPRESSOR-CELLS
T-CELLS
CANCER
CHEMOKINE
ENA-78
RECEPTORS
PROLIFERATION
ACTIVATION
PLASTICITY
IL-8
CXCL5 as Regulator of Neutrophil Function in Cutaneous Melanoma
journal article
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URL
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7ace6b0b6745e51c37ff00e759291c87
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CXCL5asRegulatorofNeutrophil_2019.pdf