The microbiome-derived metabolite TMAO drives immune activation and boosts responses to immune checkpoint blockade in pancreatic cancer.


Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
09 09 2022
Historique:
entrez: 9 9 2022
pubmed: 10 9 2022
medline: 14 9 2022
Statut: ppublish

Résumé

The composition of the gut microbiome can control innate and adaptive immunity and has emerged as a key regulator of tumor growth, especially in the context of immune checkpoint blockade (ICB) therapy. However, the underlying mechanisms for how the microbiome affects tumor growth remain unclear. Pancreatic ductal adenocarcinoma (PDAC) tends to be refractory to therapy, including ICB. Using a nontargeted, liquid chromatography-tandem mass spectrometry-based metabolomic screen, we identified the gut microbe-derived metabolite trimethylamine

Identifiants

pubmed: 36083892
doi: 10.1126/sciimmunol.abn0704
pmc: PMC9925043
mid: NIHMS1852421
doi:

Substances chimiques

Immune Checkpoint Inhibitors 0
Methylamines 0
trimethyloxamine FLD0K1SJ1A

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabn0704

Subventions

Organisme : NCI NIH HHS
ID : R01 CA057341
Pays : United States
Organisme : NIH HHS
ID : S10 OD023586
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211199
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA259240
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA252225
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA221838
Pays : United States

Commentaires et corrections

Type : CommentIn

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Auteurs

Gauri Mirji (G)

Immunology, Microenvironment and Metastasis Program, the Wistar Institute, Philadelphia, PA, USA.

Alison Worth (A)

Immunology, Microenvironment and Metastasis Program, the Wistar Institute, Philadelphia, PA, USA.

Sajad Ahmad Bhat (SA)

Immunology, Microenvironment and Metastasis Program, the Wistar Institute, Philadelphia, PA, USA.

Mohamed El Sayed (M)

Immunology, Microenvironment and Metastasis Program, the Wistar Institute, Philadelphia, PA, USA.

Toshitha Kannan (T)

Bioinformatics Facility, the Wistar Institute, Philadelphia, PA, USA.

Aaron R Goldman (AR)

Proteomics and Metabolomics Facility, the Wistar Institute, Philadelphia, PA, USA.

Hsin-Yao Tang (HY)

Proteomics and Metabolomics Facility, the Wistar Institute, Philadelphia, PA, USA.

Qin Liu (Q)

Molecular and Cellular Oncogenesis Program, the Wistar Institute, Philadelphia, PA, USA.

Noam Auslander (N)

Molecular and Cellular Oncogenesis Program, the Wistar Institute, Philadelphia, PA, USA.

Chi V Dang (CV)

Molecular and Cellular Oncogenesis Program, the Wistar Institute, Philadelphia, PA, USA.
Ludwig Institute for Cancer Research, New York, NY, USA.

Mohamed Abdel-Mohsen (M)

Immunology, Microenvironment and Metastasis Program, the Wistar Institute, Philadelphia, PA, USA.
Vaccine and Immunotherapy Center, the Wistar Institute, Philadelphia, PA, USA.

Andrew Kossenkov (A)

Bioinformatics Facility, the Wistar Institute, Philadelphia, PA, USA.

Ben Z Stanger (BZ)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Rahul S Shinde (RS)

Immunology, Microenvironment and Metastasis Program, the Wistar Institute, Philadelphia, PA, USA.

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Classifications MeSH