Autoren:	Riegel, Kristina Yurugi, Hajime Schlöder, Janine Jonuleit, Helmut Kaulich, Manuel Kirschner, Friederike Arnold-Schild, Danielle Tenzer, Stefan Schild, Hansjörg Rajalingam, Krishnaraj
Titel:	ERK5 modulates IL-6 secretion and contributes to tumor-induced immune suppression
Online-Publikationsdatum:	1-Jul-2022
Erscheinungsdatum:	2021
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	Tumors exhibit a variety of strategies to dampen antitumor immune responses. With an aim to identify factors that are secreted from tumor cells, we performed an unbiased mass spectrometry-based secretome analysis in lung cancer cells. Interleukin-6 (IL-6) has been identified as a prominent factor secreted by tumor cells and cancer-associated fibroblasts isolated from cancer patients. Incubation of dendritic cell (DC) cultures with tumor cell supernatants inhibited the production of IL-12p70 in DCs but not the surface expression of other activation markers which is reversed by treatment with IL-6 antibody. Defects in IL-12p70 production in the DCs inhibited the differentiation of Th1 but not Th2 and Th17 cells from naïve CD4+ T cells. We also demonstrate that the classical mitogen-activated protein kinase, ERK5/MAPK7, is required for IL-6 production in tumor cells. Inhibition of ERK5 activity or depletion of ERK5 prevented IL-6 production in tumor cells, which could be exploited for enhancing antitumor immune responses.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7274
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Cell death & disease 12
Seitenzahl oder Artikelnummer:	969
Verlag:	Nature Publishing Group
Verlagsort:	London u.a.
Erscheinungsdatum:	2021
ISSN:	2041-4889
DOI der Originalveröffentlichung:	10.1038/s41419-021-04257-8
Enthalten in den Sammlungen:	JGU-Publikationen