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Loss of prolyl hydroxylase-2 in myeloid cells and T-lymphocytes impairs tumor development

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dc.contributor.author Mamlouk, S.
dc.contributor.author Kalucka, J.
dc.contributor.author Singh, R.P.
dc.contributor.author Franke, K.
dc.contributor.author Muschter, A.
dc.contributor.author Langer, A.
dc.contributor.author Jakob, C.
dc.contributor.author Gassmann, M.
dc.contributor.author Baretton, G.B.
dc.contributor.author Wielockx, B.
dc.date.accessioned 2020-06-10T18:11:35Z
dc.date.available 2020-06-10T18:11:35Z
dc.date.issued 2013
dc.identifier.uri https://hdl.handle.net/20.500.12866/8009
dc.description.abstract The tumor microenvironment plays a pivotal role during cancer development and progression. The balance between suppressive and cytotoxic responses of the tumor immune microenvironment has been shown to have a direct effect on the final outcome in various human and experimental tumors. Recently, we demonstrated that the oxygen sensor HIF-prolyl hydroxylase-2 (PHD2) plays a detrimental role in tumor cells, stimulating systemic growth and metastasis in mice. In our current study, we show that the conditional ablation of PHD2 in the hematopoietic system also leads to reduced tumor volume, intriguingly generated by an imbalance between enhanced cell death and improved proliferation of tumor cells. This effect seems to rely on the overall downregulation of protumoral as well as antitumoral cytokines. Using different genetic approaches, we were able to confine this complex phenotype to the crosstalk of PHD2-deficient myeloid cells and T-lymphocytes. Taken together, our findings reveal a multifaceted role for PHD2 in several hematopoietic lineages during tumor development and might have important implications for the development of tumor therapies in the future. What's new? Here the authors describe the complex role of the oxygen sensor PHD2 in tumor-associated immune cells in a conditional PHD2-deficient mouse line. They demonstrate that the observed reduced tumor volume is a consequence of opposing changes including the drastic down-regulation of numerous pro- as well as anti-tumoral genes and an imbalance between enhanced cell death and greater proliferation of tumor cells. They confined this complex phenotype to the crosstalk of PHD2-deficient myeloid cells and T-lymphocytes. The findings reveal a multifaceted role for PHD2 in hematopoietic lineages during tumor development and might have important implications for the development of tumor therapies. en_US
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartof urn:issn:1097-0215
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject cytokines en_US
dc.subject priority journal en_US
dc.subject controlled study en_US
dc.subject article en_US
dc.subject cytokine en_US
dc.subject phenotype en_US
dc.subject animal experiment en_US
dc.subject animal model en_US
dc.subject animal tissue en_US
dc.subject nonhuman en_US
dc.subject rat en_US
dc.subject unclassified drug en_US
dc.subject mouse en_US
dc.subject down regulation en_US
dc.subject animal cell en_US
dc.subject T lymphocyte en_US
dc.subject cell proliferation en_US
dc.subject bone marrow cell en_US
dc.subject cancer size en_US
dc.subject enzyme deficiency en_US
dc.subject cancer growth en_US
dc.subject cell death en_US
dc.subject cell lineage en_US
dc.subject ablation therapy en_US
dc.subject cancer genetics en_US
dc.subject hematopoietic system en_US
dc.subject oxygenase en_US
dc.subject prolyl hydroxylase-2 en_US
dc.subject prolylhydroxylase 2 en_US
dc.subject tumor-associated immune cells en_US
dc.title Loss of prolyl hydroxylase-2 in myeloid cells and T-lymphocytes impairs tumor development en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1002/ijc.28409
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE


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