| First Author | Penny HL | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 12 | PubMed ID | 34198548 |
| Mgi Jnum | J:308910 | Mgi Id | MGI:6753465 |
| Doi | 10.3390/ijms22126350 | Citation | Penny HL, et al. (2021) Targeting Glycolysis in Macrophages Confers Protection Against Pancreatic Ductal Adenocarcinoma. Int J Mol Sci 22(12) |
| abstractText | Inflammation in the tumor microenvironment has been shown to promote disease progression in pancreatic ductal adenocarcinoma (PDAC); however, the role of macrophage metabolism in promoting inflammation is unclear. Using an orthotopic mouse model of PDAC, we demonstrate that macrophages from tumor-bearing mice exhibit elevated glycolysis. Macrophage-specific deletion of Glucose Transporter 1 (GLUT1) significantly reduced tumor burden, which was accompanied by increased Natural Killer and CD8+ T cell activity and suppression of the NLRP3-IL1beta inflammasome axis. Administration of mice with a GLUT1-specific inhibitor reduced tumor burden, comparable with gemcitabine, the current standard-of-care. In addition, we observe that intra-tumoral macrophages from human PDAC patients exhibit a pronounced glycolytic signature, which reliably predicts poor survival. Our data support a key role for macrophage metabolism in tumor immunity, which could be exploited to improve patient outcomes. |
