Targeting glycolysis in macrophages confers protection against pancreatic ductal adenocarcinoma
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Penny, Hweixian Leong
Singapore Immunology Network, A*STAR, Singapore
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Sieow, Je Lin
Singapore Immunology Network, A*STAR, Singapore
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Gun, Sin Yee
Singapore Immunology Network, A*STAR, Singapore
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Lau, Mai Chan
Singapore Immunology Network, A*STAR, Singapore
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Lee, Bernett
Singapore Immunology Network, A*STAR, Singapore
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Tan, Jasmine
Singapore Immunology Network, A*STAR, Singapore
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Phua, Cindy
Singapore Immunology Network, A*STAR, Singapore
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Toh, Florida
Singapore Immunology Network, A*STAR, Singapore
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Nga, Yvonne
Singapore Immunology Network, A*STAR, Singapore
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Yeap, Wei Hseun
Singapore Immunology Network, A*STAR, Singapore
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Janela, Baptiste
Skin Research Institute of Singapore (SRIS), Singapore
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Kumar, Dilip
Singapore Immunology Network, A*STAR, Singapore
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Chen, Hao
Singapore Immunology Network, A*STAR, Singapore
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Yeong, Joe
Singapore Immunology Network, A*STAR, Singapore
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Kenkel, Justin A.
Department of Pathology, Stanford University School of Medicine, Palo Alto CA, USA
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Pang, Angela
National University Cancer Institute Singapore, NUH Medical Centre (NUHMC), Singapore
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Lim, Diana
Department of Pathology, National University Health System, National University Hospital, Singapore
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Toh, Han Chong
National Cancer Centre, Singapore
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Hon, Tony Lim Kiat
Division of Pathology, Singapore General Hospital, Singapore
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Johnson, Christopher I.
Perkin Elmer Australia, Melbourne, Australia
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Khameneh, Hanif Javanmard
Singapore Immunology Network, A*STAR, Singapore - Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Mortellaro, Alessandra
Singapore Immunology Network, A*STAR, Singapore
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Engleman, Edgar G.
Department of Pathology, Stanford University School of Medicine, Palo Alto CA, USA
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Rotzschke, Olaf
Singapore Immunology Network, A*STAR, Singapore
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Ginhoux, Florent
Singapore Immunology Network, A*STAR, Singapore
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Abastado, Jean-Pierre
Singapore Immunology Network, A*STAR, Singapore
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Chen, Jinmiao
Singapore Immunology Network, A*STAR, Singapore
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Wong, Siew Cheng
Singapore Immunology Network, A*STAR, Singapore
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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.
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Medicine
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https://n2t.net/ark:/12658/srd1319350
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