期刊
CANCER IMMUNOLOGY RESEARCH
卷 8, 期 10, 页码 1262-1272出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-19-0904
关键词
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资金
- Goldschmidt-Jacobson Foundation
- Promedica Foundation
- Krebsliga Beider Basel (KLBB)
- Swiss National Science Foundation (SNSF) [310030-184720]
- Swiss Government Excellence Scholarships for Foreign Scholars and Artists (FCS)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Fundacao do Cancer
- Schoenemakers Foundation
- Swiss National Science Foundation (SNF) [310030_184720] Funding Source: Swiss National Science Foundation (SNF)
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.
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