Reference : The PD-L1- and IL6-mediated dampening of the IL27/STAT1 anticancer responses are prev...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/37524
The PD-L1- and IL6-mediated dampening of the IL27/STAT1 anticancer responses are prevented by a-PD-L1 or a-IL6 antibodies
English
Rolvering, Catherine mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Zimmer, Andreas David mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Ginolhac, Aurélien mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Margue, Christiane mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Kirchmeyer, Mélanie mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Servais, Florence mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Hermanns, Heike M. mailto [University Hospital Würzburg > Medical Clinic and Policlinic II, Division of Hepatology]
Hergovits, Sabine mailto [University Hospital Würzburg > Medical Clinic and Policlinic II, Division of Hepatology]
Nazarov, Petr V. mailto [Luxembourg Institute of Health - LIH > Department of Oncology, Proteome and Genome Research Unit]
Nicot, Nathalie mailto [Luxembourg Institute of Health - LIH > Department of Oncology, Proteome and Genome Research Unit]
Kreis, Stephanie mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Haan, Serge mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Haan, Claude mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
2018
Journal of Leukocyte Biology
Federation of American Societies for Experimental Biology
104
969-985
Yes
0741-5400
New York
NY
[en] cytokine ; interferon ; IFN-𝛾 ; IDO-1 ; OSM
[en] Interleukin-27 (IL27) is a type-I cytokine of the IL6/IL12 family and is predominantly secreted
by activated macrophages and dendritic cells.We show that IL27 induces STAT factor phosphorylation
in cancerous cell lines of different tissue origin. IL27 leads to STAT1 phosphorylation
and recapitulates an IFN-𝛾-like response in the microarray analyses, with up-regulation of genes
involved in antiviral defense, antigen presentation, and immune suppression. Like IFN-𝛾, IL27
leads to an up-regulation of TAP2 and MHC-I proteins, which mediate increased tumor immune
clearance. However, both cytokines also upregulate proteins such as PD-L1 (CD274) and IDO-1,
which are associatedwith immune escape of cancer. Interestingly, differential expression of these
geneswas observed within the different cell lines and when comparing IL27 to IFN-𝛾. In coculture
experiments of hepatocellular carcinoma (HCC) cells with peripheral blood mononuclear cells,
pre-treatment of the HCC cells with IL27 resulted in lowered IL2 production by anti-CD3/-CD28
activated T-lymphocytes. Addition of anti-PD-L1 antibody, however, restored IL2 secretion.
The levels of other TH1 cytokines were also enhanced or restored upon administration of
anti-PD-L1. In addition, we show that the suppression of IL27 signaling by IL6-type cytokine prestimulation—
mimicking a situation occurring, for example, in IL6-secreting tumors or in tumor
inflammation–induced cachexia—can be antagonized by antibodies against IL6-type cytokines
or their receptors. Therapeutically, the antitumor effects of IL27 (mediated, e.g., by increased
antigen presentation) might thus be increased by combining IL27with blocking antibodies against
PD-L1 or/and IL6-type cytokines.
University of Luxembourg Grants ; Deutsche Forschungs Gemeinschaft
http://hdl.handle.net/10993/37524
FnR ; FNR3975937 > Iris Behrmann > HepmiRSTAT > Inflammatory microRNAs in liver cancer > 01/09/2013 > 31/08/2016 > 2012

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