ERK5 modulates IL-6 secretion and contributes to tumor-induced immune suppression
Authors
Kristina Riegel, Hajime Yurugi, Janine Schlöder, Helmut Jonuleit, Manuel Kaulich, Friederike Kirschner, Danielle Arnold-Schild, Stefan Tenzer, Hansjörg Schild, Krishnaraj Rajalingam
Institution
University Medical Center Mainz
Country
Germany
Year
2021
Journal
Cell Death & Diseases
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.
Product use
Culture of immortalized lung epithelial cells
Tissue type
Airway
Tissue info
Immortalized human lung epithelial cells (Saleb) and KRAS transformed SALEB (SaKRAS)