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ERK1 as a therapeutic target for dendritic cell vaccination against high-grade gliomas

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Item Type:Article
Title:ERK1 as a therapeutic target for dendritic cell vaccination against high-grade gliomas
Creators Name:Ku, M.C. and Edes, I. and Bendix, I. and Pohlmann, A. and Waiczies, H. and Prozorovski, T. and Günther, M. and Martin, C. and Pagès, G. and Wolf, S.A. and Kettenmann, H. and Uckert, W. and Niendorf, T. and Waiczies, S.
Abstract:Glioma regression requires the recruitment of potent anti-tumor immune cells into the tumor microenvironment. Dendritic cells (DCs) play a role in immune responses to these tumors. The fact that DC vaccines do not effectively combat high-grade gliomas, however, suggests that DCs need to be genetically modified especially to promote their migration to tumor relevant sites. Previously, we identified extracellular signal-regulated kinase (ERK1) as a regulator of DC immunogenicity and brain autoimmunity. In the present study, we made use of modern magnetic resonance methods to study the role of ERK1 in regulating DC migration and tumor progression in a model of high-grade glioma. We found that ERK1-deficient mice are more resistant to the development of gliomas, and tumor growth in these mice is accompanied by a higher infiltration of leukocytes. ERK1-deficient DCs exhibit an increase in migration that is associated with sustained Cdc42 activation and increased expression of actin-associated cytoskeleton-organizing proteins. We also demonstrated that ERK1 deletion potentiates DC vaccination and provides a survival advantage in high-grade gliomas. Considering the therapeutic significance of these results, we propose ERK1-deleted DC vaccines as an additional means of eradicating resilient tumor cells and preventing tumor recurrence.
Keywords:ERK1, High Grade Glioma, Dendritic Cells, Cell Migration, (19)F MRI, Animals, Mice
Source:Molecular Cancer Therapeutics
Publisher:American Association for Cancer Research
Page Range:1975-1987
Date:August 2016
Official Publication:https://doi.org/10.1158/1535-7163.MCT-15-0850
PubMed:View item in PubMed

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