Metformin treatment rescues CD8

Animals CD8-Positive T-Lymphocytes / metabolism Carcinoma, Hepatocellular / metabolism Immune Checkpoint Inhibitors / pharmacology Liver / pathology Liver Neoplasms / etiology Metformin / pharmacology Mice Mice, Inbred C57BL Non-alcoholic Fatty Liver Disease / metabolism
Hepatic intravital imaging Hepatic transcriptomics Immunometabolism Liver cancer Metabolic syndrome NASH immunology

Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
09 2022
Historique:
received: 04 11 2021
revised: 08 02 2022
accepted: 03 03 2022
pubmed: 5 4 2022
medline: 23 8 2022
entrez: 4 4 2022
Statut: ppublish

Résumé

Non-alcoholic steatohepatitis (NASH) represents the fastest growing underlying cause of hepatocellular carcinoma (HCC) and has been shown to impact immune effector cell function. The standard of care for the treatment of advanced HCC is immune checkpoint inhibitor (ICI) therapy, yet NASH may negatively affect the efficacy of ICI therapy in HCC. The immunologic mechanisms underlying the impact of NASH on ICI therapy remain unclear. Herein, using multiple murine NASH models, we analysed the influence of NASH on the CD8 NASH blunted the effect of anti-PD-1 therapy against liver cancers in multiple murine models. NASH caused a proinflammatory phenotypic change of hepatic CD8 We discovered that CD8+ T-cell metabolism is critically altered in the context of NASH-related liver cancer, impacting the effectiveness of ICI therapy - a finding which has therapeutic implications in patients with NASH-related liver cancer. Non-alcoholic steatohepatitis represents the fastest growing cause of hepatocellular carcinoma. It is also associated with reduced efficacy of immunotherapy, which is the standard of care for advanced hepatocellular carcinoma. Herein, we show that non-alcoholic steatohepatitis is associated with impaired motility, metabolic function, and response to anti-PD-1 treatment in hepatic CD8

Sections du résumé

BACKGROUND & AIMS
Non-alcoholic steatohepatitis (NASH) represents the fastest growing underlying cause of hepatocellular carcinoma (HCC) and has been shown to impact immune effector cell function. The standard of care for the treatment of advanced HCC is immune checkpoint inhibitor (ICI) therapy, yet NASH may negatively affect the efficacy of ICI therapy in HCC. The immunologic mechanisms underlying the impact of NASH on ICI therapy remain unclear.
METHODS
Herein, using multiple murine NASH models, we analysed the influence of NASH on the CD8
RESULTS
NASH blunted the effect of anti-PD-1 therapy against liver cancers in multiple murine models. NASH caused a proinflammatory phenotypic change of hepatic CD8
CONCLUSIONS
We discovered that CD8+ T-cell metabolism is critically altered in the context of NASH-related liver cancer, impacting the effectiveness of ICI therapy - a finding which has therapeutic implications in patients with NASH-related liver cancer.
LAY SUMMARY
Non-alcoholic steatohepatitis represents the fastest growing cause of hepatocellular carcinoma. It is also associated with reduced efficacy of immunotherapy, which is the standard of care for advanced hepatocellular carcinoma. Herein, we show that non-alcoholic steatohepatitis is associated with impaired motility, metabolic function, and response to anti-PD-1 treatment in hepatic CD8

Identifiants

DOI: 10.1016/j.jhep.2022.03.010 PMID: 35378172 PMC: PMC9391315
pubmed: 35378172
pii: S0168-8278(22)00178-7
doi: 10.1016/j.jhep.2022.03.010
pmc: PMC9391315
mid: NIHMS1817664
pii:
doi:

Substances chimiques

Immune Checkpoint Inhibitors 0
Metformin 9100L32L2N

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

748-760

Subventions

Organisme : Intramural NIH HHS
ID : ZIA BC011345
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC011346
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Conflicts of interest The authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details.

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Auteurs

Simon Wabitsch (S)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Justin D McCallen (JD)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Olena Kamenyeva (O)

Biological Imaging Section, Research Technology Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.

Benjamin Ruf (B)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

John C McVey (JC)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Juraj Kabat (J)

Biological Imaging Section, Research Technology Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.

Juliane S Walz (JS)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Yaron Rotman (Y)

Liver and Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

Kylynda C Bauer (KC)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Amanda J Craig (AJ)

Laboratory of Human Carcinogenesis, Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Marie Pouzolles (M)

Basic to Translation Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Ira Phadke (I)

Basic to Translation Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Vanessa Catania (V)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Benjamin L Green (BL)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Claude Fu (C)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Laurence P Diggs (LP)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Bernd Heinrich (B)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Xin Wei Wang (XW)

Laboratory of Human Carcinogenesis, Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; NCI CCR Liver Cancer Program, National Institutes of Health, Bethesda, MD, USA.

Chi Ma (C)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Tim F Greten (TF)

Gastrointestinal Malignancy Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; NCI CCR Liver Cancer Program, National Institutes of Health, Bethesda, MD, USA. Electronic address: Tim.greten@nih.gov.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Metformin treatment rescues CD8
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Metformin treatment rescues CD8
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Carcinome hépatocellulaire › Metformin treatment rescues CD8
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Inhibiteurs de points de contrôle immunitaires › Metformin treatment rescues CD8
questionsmedicales.fr › Système digestif › Foie › Metformin treatment rescues CD8
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Metformin treatment rescues CD8
questionsmedicales.fr › Composés chimiques organiques › Amidines › Guanidines › Biguanides › Metformine › Metformin treatment rescues CD8
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Metformin treatment rescues CD8
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Metformin treatment rescues CD8
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Stéatose hépatique › Stéatose hépatique non alcoolique › Metformin treatment rescues CD8