Eloïne Bestion, Madani Rachid, Annemilaï Tijeras-Raballand, Gael Roth, Thomas Decaens, Christelle Ansaldi, Soraya Mezouar, Eric Raymond, Philippe Halfon
{"title":"棕榈酰蛋白硫酯酶-1抑制剂Ezurpimtrostat与PD-1抑制剂联合使用可使肝细胞癌中的CD8+淋巴细胞重新增殖。","authors":"Eloïne Bestion, Madani Rachid, Annemilaï Tijeras-Raballand, Gael Roth, Thomas Decaens, Christelle Ansaldi, Soraya Mezouar, Eric Raymond, Philippe Halfon","doi":"10.1007/s11523-023-01019-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Palmitoyl-protein thioesterase-1 (PPT1) is a clinical stage druggable target for inhibiting autophagy in cancer.</p><p><strong>Objective: </strong>We aimed to determine the cellular and molecular activity of targeting PPT1 using ezurpimtrostat, in combination with an anti-PD-1 antibody.</p><p><strong>Methods: </strong>In this study we used a transgenic immunocompetent mouse model of hepatocellular carcinoma.</p><p><strong>Results: </strong>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<sup>+</sup> lymphocytes.</p><p><strong>Conclusions: </strong>Ezurpimtrostat turns cold tumors into hot tumors and, thus, could improve T cell-mediated immunotherapies in liver cancer.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ezurpimtrostat, A Palmitoyl-Protein Thioesterase-1 Inhibitor, Combined with PD-1 Inhibition Provides CD8<sup>+</sup> 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\",\"doi\":\"10.1007/s11523-023-01019-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Palmitoyl-protein thioesterase-1 (PPT1) is a clinical stage druggable target for inhibiting autophagy in cancer.</p><p><strong>Objective: </strong>We aimed to determine the cellular and molecular activity of targeting PPT1 using ezurpimtrostat, in combination with an anti-PD-1 antibody.</p><p><strong>Methods: </strong>In this study we used a transgenic immunocompetent mouse model of hepatocellular carcinoma.</p><p><strong>Results: </strong>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<sup>+</sup> lymphocytes.</p><p><strong>Conclusions: </strong>Ezurpimtrostat turns cold tumors into hot tumors and, thus, could improve T cell-mediated immunotherapies in liver cancer.</p>\",\"PeriodicalId\":22195,\"journal\":{\"name\":\"Targeted Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Targeted Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11523-023-01019-8\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/12/22 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Targeted Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11523-023-01019-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Ezurpimtrostat, A Palmitoyl-Protein Thioesterase-1 Inhibitor, Combined with PD-1 Inhibition Provides CD8+ Lymphocyte Repopulation in Hepatocellular Carcinoma.
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.
期刊介绍：
Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes:
Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches.
Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways.
Current Opinion articles that place interesting areas in perspective.
Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations.
Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement.
Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.
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