DGKζ exerts greater control than DGKα over CD8+ T cell activity and tumor inhibition. Oncoimmunology 2021;10(1):1941566
Date
08/06/2021Pubmed ID
34350062Pubmed Central ID
PMC8296965DOI
10.1080/2162402X.2021.1941566Scopus ID
2-s2.0-85110698608 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Two isoforms of diacylglycerol kinases (DGKs), DGKα and DGKζ, are primarily responsible for terminating DAG-mediated activation of Ras and PKCθ pathways in T cells. A direct comparison of tumor growth between mice lacking each isoform has not been undertaken. We evaluated the growth of three syngeneic tumor cell lines in mice lacking either DGKα or DGKζ in the presence or absence of treatment with anti-PD1 and determined that (i) mice deficient in DGKζ conferred enhanced control of tumor relative to mice deficient in DGKα and (ii) deficiency of DGKζ acted additively with anti-PD1 in tumor control. Consistent with this finding, functional and RNA-sequencing analyses revealed greater changes in stimulated DGKζ-deficient T cells compared with DGKα-deficient T cells, which were enhanced relative to wildtype T cells. DGKζ also imparted greater regulation than DGKα in human T cells. Together, these data support targeting the ζ isoform of DGKs to therapeutically enhance T cell anti-tumor activity.
Author List
Gu J, Wang C, Cao C, Huang J, Holzhauer S, Desilva H, Wesley EM, Evans DB, Benci J, Wichroski M, Wee S, Riese MJAuthor
Douglas B. Evans MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD8-Positive T-Lymphocytes
Cell Line, Tumor
Diacylglycerol Kinase
Mice
T-Lymphocytes
