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Front Cell Dev Biol. 2016 Oct 17;4:108. eCollection 2016.

Diacylglycerol Kinases (DGKs): Novel Targets for Improving T Cell Activity in Cancer.

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Division of Hematology/Oncology, Department of Medicine, Medical College of WisconsinMilwaukee, WI, USA; Blood Center of Wisconsin, Blood Research InstituteMilwaukee, WI, USA.
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Philadelphia, PA, USA.
Division of Hematology/Oncology/Transplant, Department of Pediatrics, Medical College of Wisconsin Milwaukee, WI, USA.


Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the metabolism of diacylglycerol (DAG). Two isoforms of DGK, DGKα, and DGKζ, specifically regulate the pool of DAG that is generated as a second messenger after stimulation of the T cell receptor (TCR). Deletion of either isoform in mouse models results in T cells bearing a hyperresponsive phenotype and enhanced T cell activity against malignancy. Whereas, DGKζ appears to be the dominant isoform in T cells, rationale exists for targeting both isoforms individually or coordinately. Additional work is needed to rigorously identify the molecular changes that result from deletion of DGKs in order to understand how DAG contributes to T cell activation, the effect of DGK inhibition in human T cells, and to rationally develop combined immunotherapeutic strategies that target DGKs.


CD8+ T cell; T cell receptor; diacylglycerol; diacylglycerol kinase; immunotherapy

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