Penny, Hweixian Leong Sieow, Je Lin Gun, Sin Yee Lau, Mai Chan Lee, Bernett Tan, Jasmine Phua, Cindy Toh, Florida Nga, Yvonne Yeap, Wei Hseun Janela, Baptiste Kumar, Dilip Chen, Hao Yeong, Joe Kenkel, Justin A. Pang, Angela Lim, Diana Toh, Han Chong Hon, Tony Lim Kiat Johnson, Christopher I. Khameneh, Hanif Javanmard Mortellaro, Alessandra Engleman, Edgar G. Rotzschke, Olaf Ginhoux, Florent Abastado, Jean-Pierre Chen, Jinmiao Wong, Siew Cheng 2021-06-14 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. application/pdf https://localhost:5000/ark:/12658/srd1319350 https://susi.usi.ch/global/documents/319350 https://susi.usi.ch/documents/319350/files/Khameneh_ijms_2021.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms22126350 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319350 info:eu-repo/semantics/openAccess CC BY International journal of molecular sciences. - MDPI. - 2021, vol. 22, no. 12, p. 24 Pancreatic ductal adenocarcinoma Macrophage Immunometabolism Glycolysis info:eu-repo/classification/udc/61 Targeting glycolysis in macrophages confers protection against pancreatic ductal adenocarcinoma http://purl.org/coar/resource_type/c_6501