PDCD4-bound mRNA profile in T lymphocytes

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dc.contributor.authorLingel, Holger
dc.contributor.authorSchanze, Denny
dc.contributor.authorZenker, Martin
dc.contributor.authorBrunner-Weinzierl, Monika
dc.date.accessioned2018-11-22T13:09:11Z
dc.date.available2018-11-22T13:09:11Z
dc.date.issued2017
dc.description.abstractThe blockade of inhibitory receptors such as CTLA-4 (CD152) is being used as immune-checkpoint therapy, offering a powerful strategy to restore effective immune responses against tumors. To determine signal components that are induced under the control of CTLA-4 we analyzed activated murine CD8+ T cells by quantitative proteomics. Accurate mass spectrometry revealed that CTLA-4 engagement led to central changes in the phosphorylation of proteins involved in T-cell differentiation. Beside other targets, we discovered a CTLA-4-mediated induction of the translational inhibitor programmed cell death-4 (PDCD4) as a result of FoxO1 nuclear re-localization. PDCD4 further bound a distinct set of mRNAs including Glutaminase, which points out a critical role for CTLA-4 in CD8+ T-cell metabolism. Consequently, PDCD4-deficient cytotoxic T-lymphocytes (CTLs) expressed increased amounts of otherwise repressed effector molecules and ultimately led to superior control of tumor growth in vivo. These findings reveal a novel CTLA-4-mediated pathway to attenuate CTLs and indicate the importance of post-transcriptional mechanisms in the regulation of anti-tumor immune responses.en_US
dc.identifier.urihttp://open-science.ub.ovgu.de/xmlui/handle/684882692/11
dc.identifier.urihttps://doi.org/10.24352/UB.OVGU-2020-137
dc.language.isoenen_US
dc.publisherUniversitätskinderklinik (HL, MB-W) und Institut für Genetik (DS, MZ), Medizinische Fakultät, OVGU Magdeburgen_US
dc.rights.urihttps://creativecommons.org/licenses/by-sa/4.0/
dc.subjectmRNAen_US
dc.subjectRNA-Expressen_US
dc.titlePDCD4-bound mRNA profile in T lymphocytesen_US
dc.typeDataseten_US

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