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Targeted Oncology
Published in: Targeted Oncology 1/2024

22-12-2023 | Hepatocellular Carcinoma | Original Research Article

Ezurpimtrostat, A Palmitoyl-Protein Thioesterase-1 Inhibitor, Combined with PD-1 Inhibition Provides CD8+ Lymphocyte Repopulation in Hepatocellular Carcinoma

Authors: Eloïne Bestion, Madani Rachid, Annemilaï Tijeras-Raballand, Gael Roth, Thomas Decaens, Christelle Ansaldi, Soraya Mezouar, Eric Raymond, Philippe Halfon

Published in: Targeted Oncology | Issue 1/2024

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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.

Graphical Abstract

Appendix
Available only for authorised users
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Metadata
Title
Ezurpimtrostat, A Palmitoyl-Protein Thioesterase-1 Inhibitor, Combined with PD-1 Inhibition Provides CD8+ Lymphocyte Repopulation in Hepatocellular Carcinoma
Authors
Eloïne Bestion
Madani Rachid
Annemilaï Tijeras-Raballand
Gael Roth
Thomas Decaens
Christelle Ansaldi
Soraya Mezouar
Eric Raymond
Philippe Halfon
Publication date
22-12-2023
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 1/2024
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-023-01019-8

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