Hyperglycemia Enhances Cancer Immune Evasion by Inducing Alternative Macrophage Polarization through Increased O-GlcNAcylation.
Journal
Cancer immunology research
ISSN: 2326-6074
Titre abrégé: Cancer Immunol Res
Pays: United States
ID NLM: 101614637
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
14
11
2019
revised:
25
04
2020
accepted:
21
07
2020
pubmed:
21
8
2020
medline:
10
9
2021
entrez:
22
8
2020
Statut:
ppublish
Résumé
Diabetes mellitus (DM) significantly increases the risk for cancer and cancer progression. Hyperglycemia is the defining characteristic of DM and tightly correlates with a poor prognosis in patients with cancer. The hexosamine biosynthetic pathway (HBP) is emerging as a pivotal cascade linking high glucose, tumor progression, and impaired immune function. Here we show that enhanced glucose flow through the HBP drives cancer progression and immune evasion by increasing O-GlcNAcylation in tumor-associated macrophages (TAM). Increased O-GlcNAc skewed macrophage polarization to a M2-like phenotype supporting tumor progression. Finally, we found an upregulation of M2 markers on TAMs in DM2 patients with colorectal cancer compared with nondiabetic normoglycemic patients. Our results provide evidence for a new and targetable mechanism of cancer immune evasion in patients with hyperglycemia, advocating for strict control of hyperglycemia in patients with cancer.
Identifiants
pubmed: 32819969
pii: 2326-6066.CIR-19-0904
doi: 10.1158/2326-6066.CIR-19-0904
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1262-1272Informations de copyright
©2020 American Association for Cancer Research.