Ezurpimtrostat, A Palmitoyl-Protein Thioesterase-1 Inhibitor, Combined with PD-1 Inhibition Provides CD8+ Lymphocyte Repopulation in Hepatocellular Carcinoma.
Target Oncol
; 19(1): 95-106, 2024 Jan.
Article
in En
| MEDLINE
| ID: mdl-38133710
ABSTRACT
BACKGROUND:
Palmitoyl-protein thioesterase-1 (PPT1) is a clinical stage druggable target for inhibiting autophagy in cancer.OBJECTIVE:
We aimed to determine the cellular and molecular activity of targeting PPT1 using ezurpimtrostat, in combination with an anti-PD-1 antibody.METHODS:
In this study we used a transgenic immunocompetent mouse model of hepatocellular carcinoma.RESULTS:
Herein, we revealed that inhibition of PPT1 using ezurpimtrostat decreased the liver tumor burden in a mouse model of hepatocellular carcinoma by inducing the penetration of lymphocytes into tumors when combined with anti-programmed death-1 (PD-1). Inhibition of PPT1 potentiates the effects of anti-PD-1 immunotherapy by increasing the expression of major histocompatibility complex (MHC)-I at the surface of liver cancer cells and modulates immunity through recolonization and activation of cytotoxic CD8+ lymphocytes.CONCLUSIONS:
Ezurpimtrostat turns cold tumors into hot tumors and, thus, could improve T cell-mediated immunotherapies in liver cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiolester Hydrolases
/
Carcinoma, Hepatocellular
/
Liver Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Target Oncol
Journal subject:
NEOPLASIAS
Year:
2024
Document type:
Article
Affiliation country:
France