DGKα/ζ inhibition lowers the TCR affinity threshold and potentiates antitumor immunity.

ABSTRACT: Diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG) signaling by converting DAG to phosphatidic acid, thereby suppressing pathways downstream of T cell receptor signaling. Using a dual DGKα/ζ inhibitor (DGKi), tumor-specific CD8 T cells with different affinities (TRP1^high and TRP1^low), and altered peptide ligands, we demonstrate that inhibition of DGKα/ζ can lower the signaling threshold for T cell priming. TRP1^high and TRP1^low CD8 T cells produced more effector cytokines in the presence of cognate antigen and DGKi. Effector TRP1^high- and TRP1^low-mediated cytolysis of tumor cells with low antigen load required antigen recognition, was mediated by interferon-γ, and augmented by DGKi. Adoptive T cell transfer into mic

SUBMITTER: Kureshi R 

PROVIDER: S-EPMC10672170 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature