Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 4, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2016.00108
Keywords
diacylglycerol; diacylglycerol kinase; immunotherapy; CD8+T cell; T cell receptor
Categories
Funding
- NIH [K08 CA151893, K08 CA163941]
- American Cancer Society
- HRHM Program of MACC Fund
- Kathy Duffey Fogerty Family Foundation
- NATIONAL CANCER INSTITUTE [K08CA163941] Funding Source: NIH RePORTER
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Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the metabolism of diacylglycerol (DAG). Two isoforms of DGK, DGK alpha, and DGK zeta, 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, DGK zeta 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.
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