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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
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Cell death & disease
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

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