Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.
APOC2
lipolysis
lysine‐lactylation
non‐small cell lung cancer
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
09 Jul 2024
09 Jul 2024
Historique:
received:
08
06
2024
medline:
9
7
2024
pubmed:
9
7
2024
entrez:
9
7
2024
Statut:
aheadofprint
Résumé
Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2
Identifiants
pubmed: 38981044
doi: 10.1002/advs.202406333
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2406333Subventions
Organisme : National Natural Science Foundation of China
ID : 32270749
Organisme : National Natural Science Foundation of China
ID : 32070770
Organisme : National Natural Science Foundation of China
ID : 31970720
Organisme : National Natural Science Foundation of China
ID : 3197050071
Organisme : National Natural Science Foundation of China
ID : 82272875
Organisme : National Natural Science Foundation of China
ID : 81702337
Organisme : Shanghai Rising-Star Program
Organisme : Original exploration project of Shanghai Natural Science Foundation
ID : 23ZR1480600
Organisme : Health and Family Planning Commission of Shanghai Municipality
ID : 20224Y0067
Organisme : Shanghai "Rising Stars of Medical Talent" Youth Development Program Youth Medical Talents - Specialist Program
Informations de copyright
© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.
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