Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
03
05
2023
accepted:
30
06
2023
medline:
25
9
2023
pubmed:
4
8
2023
entrez:
3
8
2023
Statut:
ppublish
Résumé
Restriction of methionine (MR), a sulfur-containing essential amino acid, has been reported to repress cancer growth and improve therapeutic responses in several preclinical settings. However, how MR impacts cancer progression in the context of the intact immune system is unknown. Here we report that while inhibiting cancer growth in immunocompromised mice, MR reduces T cell abundance, exacerbates tumour growth and impairs tumour response to immunotherapy in immunocompetent male and female mice. Mechanistically, MR reduces microbial production of hydrogen sulfide, which is critical for immune cell survival/activation. Dietary supplementation of a hydrogen sulfide donor or a precursor, or methionine, stimulates antitumour immunity and suppresses tumour progression. Our findings reveal an unexpected negative interaction between MR, sulfur deficiency and antitumour immunity and further uncover a vital role of gut microbiota in mediating this interaction. Our study suggests that any possible anticancer benefits of MR require careful consideration of both the microbiota and the immune system.
Identifiants
pubmed: 37537369
doi: 10.1038/s42255-023-00854-3
pii: 10.1038/s42255-023-00854-3
pmc: PMC10513933
mid: NIHMS1925260
doi:
Substances chimiques
Methionine
AE28F7PNPL
Hydrogen Sulfide
YY9FVM7NSN
Racemethionine
73JWT2K6T3
Sulfur
70FD1KFU70
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1526-1543Subventions
Organisme : NIGMS NIH HHS
ID : FI2 GM143339
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI160774
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA ES102205
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM143024
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG071256
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI123193
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES031007
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG076019
Pays : United States
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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