Targeting glycolysis in macrophages confers protection against pancreatic ductal adenocarcinoma
- Penny, Hweixian Leong Singapore Immunology Network, A*STAR, Singapore
- Sieow, Je Lin Singapore Immunology Network, A*STAR, Singapore
- Gun, Sin Yee Singapore Immunology Network, A*STAR, Singapore
- Lau, Mai Chan Singapore Immunology Network, A*STAR, Singapore
- Lee, Bernett Singapore Immunology Network, A*STAR, Singapore
- Tan, Jasmine Singapore Immunology Network, A*STAR, Singapore
- Phua, Cindy Singapore Immunology Network, A*STAR, Singapore
- Toh, Florida Singapore Immunology Network, A*STAR, Singapore
- Nga, Yvonne Singapore Immunology Network, A*STAR, Singapore
- Yeap, Wei Hseun Singapore Immunology Network, A*STAR, Singapore
- Janela, Baptiste Skin Research Institute of Singapore (SRIS), Singapore
- Kumar, Dilip Singapore Immunology Network, A*STAR, Singapore
- Chen, Hao Singapore Immunology Network, A*STAR, Singapore
- Yeong, Joe Singapore Immunology Network, A*STAR, Singapore
- Kenkel, Justin A. Department of Pathology, Stanford University School of Medicine, Palo Alto CA, USA
- Pang, Angela National University Cancer Institute Singapore, NUH Medical Centre (NUHMC), Singapore
- Lim, Diana Department of Pathology, National University Health System, National University Hospital, Singapore
- Toh, Han Chong National Cancer Centre, Singapore
- Hon, Tony Lim Kiat Division of Pathology, Singapore General Hospital, Singapore
- Johnson, Christopher I. Perkin Elmer Australia, Melbourne, Australia
- Khameneh, Hanif Javanmard Singapore Immunology Network, A*STAR, Singapore - Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
- Mortellaro, Alessandra Singapore Immunology Network, A*STAR, Singapore
- Engleman, Edgar G. Department of Pathology, Stanford University School of Medicine, Palo Alto CA, USA
- Rotzschke, Olaf Singapore Immunology Network, A*STAR, Singapore
- Ginhoux, Florent Singapore Immunology Network, A*STAR, Singapore
- Abastado, Jean-Pierre Singapore Immunology Network, A*STAR, Singapore
- Chen, Jinmiao Singapore Immunology Network, A*STAR, Singapore
- Wong, Siew Cheng Singapore Immunology Network, A*STAR, Singapore
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14.06.2021
Published in:
- International journal of molecular sciences. - MDPI. - 2021, vol. 22, no. 12, p. 24
English
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-IL1β 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.
- Language
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- English
- Classification
- Medicine
- License
- License undefined
- Identifiers
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- RERO DOC 333697
- DOI 10.3390/ijms22126350
- ARK ark:/12658/srd1319350
- Persistent URL
- https://n2t.net/ark:/12658/srd1319350
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