Authors:	Riegel, Kristina Yurugi, Hajime Schlöder, Janine Jonuleit, Helmut Kaulich, Manuel Kirschner, Friederike Arnold-Schild, Danielle Tenzer, Stefan Schild, Hansjörg Rajalingam, Krishnaraj
Title:	ERK5 modulates IL-6 secretion and contributes to tumor-induced immune suppression
Online publication date:	1-Jul-2022
Year of first publication:	2021
Language:	english
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:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7274
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Cell death & disease 12
Pages or article number:	969
Publisher:	Nature Publishing Group
Publisher place:	London u.a.
Issue date:	2021
ISSN:	2041-4889
Publisher DOI:	10.1038/s41419-021-04257-8
Appears in collections:	JGU-Publikationen