Perioperative arginine prevents metastases by accelerating natural killer cell recovery after surgery.
arginine
colorectal cancer
immunology
immunotherapy
metastasis
myeloid-derived suppressor cells
natural killer cells
surgery
surgical oncology
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
05 10 2022
05 10 2022
Historique:
received:
02
06
2021
revised:
21
05
2022
accepted:
21
05
2022
pubmed:
28
5
2022
medline:
12
10
2022
entrez:
27
5
2022
Statut:
ppublish
Résumé
Profound natural killer (NK) cell suppression after cancer surgery is a main driver of metastases and recurrence, for which there is no clinically approved intervention available. Surgical stress is known to cause systemic postoperative changes that negatively modulate NK cell function including the expansion of surgery-induced myeloid-derived suppressor cells (Sx-MDSCs) and a marked reduction in arginine bioavailability. In this study, we determine that Sx-MDSCs regulate systemic arginine levels in the postoperative period and that restoring arginine imbalance after surgery by dietary intake alone was sufficient to significantly reduce surgery-induced metastases in our preclinical murine models. Importantly, the effects of perioperative arginine were dependent upon NK cells. Although perioperative arginine did not prevent immediate NK cell immunoparalysis after surgery, it did accelerate their return to preoperative cytotoxicity, interferon gamma secretion, and activating receptor expression. Finally, in a cohort of patients with colorectal cancer, postoperative arginine levels were shown to correlate with their Sx-MDSC levels. Therefore, this study lends further support for the use of perioperative arginine supplementation by improving NK cell recovery after surgery.
Identifiants
pubmed: 35619558
pii: S1525-0016(22)00322-7
doi: 10.1016/j.ymthe.2022.05.024
pmc: PMC9552810
pii:
doi:
Substances chimiques
Interferon-gamma
82115-62-6
Arginine
94ZLA3W45F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3270-3283Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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