Combination therapy for hepatocellular carcinoma with diacylglycerol kinase alpha inhibition and anti-programmed cell death-1 ligand blockade.

ABSTRACT: Activation of diacylglycerol kinase alpha (DGKα) augments proliferation and suppresses apoptosis of cancer cells and induces T lymphocyte anergy. We investigated the dual effects of DGKα inhibition on tumorigenesis and anti-tumor immunity with the aim of establishing a novel therapeutic strategy for cancer. We examined the effects of a DGKα inhibitor (DGKAI) on liver cancer cell proliferation and cytokine production by immune cells in vitro and on tumorigenesis and host immunity in a hepatocellular carcinoma (HCC) mouse model. Oral DGKAI significantly suppressed tumor growth and prolonged survival in model mice. Tumor infiltration of T cells and dendritic cells was also enhanced in mice treated with DGKAI, and the production of cytokines and cytotoxic molecules by CD4⁺ and CD8

SUBMITTER: Okada N 

PROVIDER: S-EPMC10991887 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature