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Human innate immune cell crosstalk induces melanoma cell senescence

Funck, Felix; Pahl, Jens; Kyjacova, Lenka; Freund, Lukas; Oehrl, Stephanie; Gräbe, Galina; Pezer, Silvia; Hassel, Jessica C.; Sleeman, Jonathan; Cerwenka, Adelheid; Schäkel, Knut

Mononuclear phagocytes and NK cells constitute the first line of innate immune defense. How these cells interact and join forces against cancer is incompletely understood. Here, we observed an early accumulation of slan$^{+}$ (6-sulfo LacNAc) non-classical monocytes (slanMo) in stage I melanoma, which was followed by an increase in NK cell numbers in stage III. Accordingly, culture supernatants of slanMo induced migration of primary human NK cells in vitro via the chemotactic cytokine IL-8 (CXCL8), suggesting a role for slanMo in NK cell recruitment into cancer tissues. High levels of TNF-α and IFN-γ were produced in co-cultures of TLR-ligand stimulated slanMo and NK cells, whereas much lower levels were contained in cultures of slanMo and NK cells alone. Moreover, TNF-α and IFN-γ concentrations in slanMo/NK cell co-cultures exceeded those in CD14$^{+}$ monocyte/NK cell and slanMo/T cell co-cultures. Importantly, TNF-α and IFN-γ that was produced in TLR-ligand stimulated slanMo/NK cell co-cultures induced senescence in different melanoma cell lines, as indicated by reduced melanoma cell proliferation, increased senescence-associated β-galactosidase expression, p21 upregulation, and induction of a senescence-associated secretory phenotype (SASP). ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000127786
Veröffentlicht am 29.12.2021
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 2162-402X
KITopen-ID: 1000127786
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in OncoImmunology
Verlag Taylor & Francis Open Access
Band 9
Heft 1
Seiten Article-Nr.: 1808424
Vorab online veröffentlicht am 30.08.2020
Schlagwörter slanMo, NK cell, melanoma, senescence, cytokines
Nachgewiesen in Web of Science
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