PMID- 38133710
OWN - NLM
STAT- MEDLINE
DCOM- 20240201
LR  - 20240320
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 19
IP  - 1
DP  - 2024 Jan
TI  - Ezurpimtrostat, A Palmitoyl-Protein Thioesterase-1 Inhibitor, Combined with PD-1 
      Inhibition Provides CD8(+) Lymphocyte Repopulation in Hepatocellular Carcinoma.
PG  - 95-106
LID - 10.1007/s11523-023-01019-8 [doi]
AB  - 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.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Bestion, Eloine
AU  - Bestion E
AD  - Genoscience Pharma, 10, Rue d'Iena, 13006, Marseille, France.
FAU - Rachid, Madani
AU  - Rachid M
AD  - Genoscience Pharma, 10, Rue d'Iena, 13006, Marseille, France.
FAU - Tijeras-Raballand, Annemilai
AU  - Tijeras-Raballand A
AD  - AFR Oncologie, Boulogne-Billancourt, France.
FAU - Roth, Gael
AU  - Roth G
AD  - Centre hospitalouniversitaire Grenoble Alpes/Institute for Advanced Biosciences, 
      Centre national de la recherche scienti-fique, Unite mixte de recherche 
      5309-Institut national de la sante et de la recherche medicale U1209, University 
      Grenoble Alpes/Hepato-Gastroenterology and Digestive Oncology Department, 38043, 
      Grenoble, France.
FAU - Decaens, Thomas
AU  - Decaens T
AD  - Centre hospitalouniversitaire Grenoble Alpes/Institute for Advanced Biosciences, 
      Centre national de la recherche scienti-fique, Unite mixte de recherche 
      5309-Institut national de la sante et de la recherche medicale U1209, University 
      Grenoble Alpes/Hepato-Gastroenterology and Digestive Oncology Department, 38043, 
      Grenoble, France.
FAU - Ansaldi, Christelle
AU  - Ansaldi C
AD  - Genoscience Pharma, 10, Rue d'Iena, 13006, Marseille, France.
FAU - Mezouar, Soraya
AU  - Mezouar S
AUID- ORCID: 0000-0002-2285-7051
AD  - Genoscience Pharma, 10, Rue d'Iena, 13006, Marseille, France.
AD  - Etablissement francais du sang, Centre national de la recherche scientifique, 
      Anthropologie bio-culturelle, droit, ethique et sante, "Biologie des Groupes 
      Sanguins", Aix-Marseille University, Marseille, France.
FAU - Raymond, Eric
AU  - Raymond E
AD  - Genoscience Pharma, 10, Rue d'Iena, 13006, Marseille, France.
AD  - Oncology Department, Groupe Hospitalier Paris Saint Joseph, Paris, France.
FAU - Halfon, Philippe
AU  - Halfon P
AD  - Genoscience Pharma, 10, Rue d'Iena, 13006, Marseille, France. 
      phalfon@genosciencepharma.com.
LA  - eng
PT  - Journal Article
DEP - 20231222
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
SB  - IM
MH  - Mice
MH  - Humans
MH  - Animals
MH  - *Carcinoma, Hepatocellular/drug therapy/pathology
MH  - *Liver Neoplasms/drug therapy/pathology
MH  - Programmed Cell Death 1 Receptor
MH  - Mice, Transgenic
MH  - CD8-Positive T-Lymphocytes/metabolism/pathology
MH  - Lymphocytes/metabolism
MH  - *Thiolester Hydrolases
EDAT- 2023/12/22 12:41
MHDA- 2024/02/01 06:42
CRDT- 2023/12/22 11:14
PHST- 2023/11/20 00:00 [accepted]
PHST- 2024/02/01 06:42 [medline]
PHST- 2023/12/22 12:41 [pubmed]
PHST- 2023/12/22 11:14 [entrez]
AID - 10.1007/s11523-023-01019-8 [pii]
AID - 10.1007/s11523-023-01019-8 [doi]
PST - ppublish
SO  - Target Oncol. 2024 Jan;19(1):95-106. doi: 10.1007/s11523-023-01019-8. Epub 2023 
      Dec 22.