English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Acetate Promotes T Cell Effector Function during Glucose Restriction

Qiu, J., Villa, M., Sanin, P. D. E., Buck, M. D., O’Sullivan, D., Ching, R. W., et al. (2019). Acetate Promotes T Cell Effector Function during Glucose Restriction. Cell Reports, 27, 2063-2074. doi:10.1016/j.celrep.2019.04.022.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
Qui et al..pdf (Publisher version), 5MB
 
File Permalink:
-
Name:
Qui et al..pdf
Description:
-
Visibility:
Restricted (Max Planck Institute of Immunobiology and Epigenetics, MFIB; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
2019
Copyright Info:
-

Creators

show
hide
 Creators:
Qiu, Jing1, Author
Villa, Matteo1, Author              
Sanin, Pena David Estaban1, Author              
Buck, Michael D.1, Author
O’Sullivan, David1, Author
Ching, Reagan W.2, Author              
Matsushita, Mai1, Author
Grzes, Katarzyna1, Author              
Winkler, Frances3, Author
Chang, Chih-Hao3, Author
Jonathan, D. Curtis1, Author              
Kyle, Ryan L.1, Author
Bakker, Nikki Van Teijlingen1, Author
Corrado, Mauro1, Author              
Haessler, Fabian1, Author
Alfei, Francesca3, Author
Edwards-Hicks, Joy1, Author
Maggi Jr., Leonard B.3, Author
Zehn, Dietmar3, Author
Egawa, Takeshi3, Author
Bengsch, Bertram3, AuthorKlein-Geltink, Ramon1, Author              Jenuwein, Thomas2, Author              Pearce, Edward Jonathen1, Author              Pearce, Erika Laine1, Author               more..
Affiliations:
1Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243640              
2Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243640              
3External Organizations, ou_persistent22              

Content

show
hide
Free keywords: T cell exhaustion, T cell hyporesponsiveness, T cells, acetate, acetyl-CoA synthetase, chromatin remodeling, effector functions, tumor immunity, tumor-infiltrating lymphocytes
 Abstract: Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation to the surrounding microenvironment is therefore key for maintaining appropriate cell function. For instance, cancer cells use acetate as a substrate alternative to glucose to fuel metabolism and growth. Here, we show that acetate rescues effector function in glucose-restricted CD8+ T cells. Mechanistically, acetate promotes histone acetylation and chromatin accessibility and enhances IFN-γ gene transcription and cytokine production in an acetyl-CoA synthetase (ACSS)-dependent manner. Ex vivo acetate treatment increases IFN-γ production by exhausted T cells, whereas reducing ACSS expression in T cells impairs IFN-γ production by tumor-infiltrating lymphocytes and tumor clearance. Thus, hyporesponsive T cells can be epigenetically remodeled and reactivated by acetate, suggesting that pathways regulating the use of substrates alternative to glucose could be therapeutically targeted to promote T cell function during cancer.

Details

show
hide
Language(s): eng - English
 Dates: 2019-05-19
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.celrep.2019.04.022
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Cell Reports
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 27 Sequence Number: - Start / End Page: 2063 - 2074 Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247