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Title: Metabolic reprogramming of tumor-infiltrating myeloid cells conveys protection against pancreatic ductal adenocarcinoma
Authors: Sieow, Je Lin
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2018
Source: Sieow, J. L. (2018). Metabolic reprogramming of tumor-infiltrating myeloid cells conveys protection against pancreatic ductal adenocarcinoma. Doctoral thesis, Nanyang Technological University, Singapore.
Abstract: Myriad mechanisms of immune evasion contribute to therapeutic resistance of pancreatic cancer and poor survival. While it is well established that tumor cells exhibit the Warburg effect for energy production, the contribution of myeloid cell metabolism to disease progression is unknown. In this study, we highlight the importance of immunometabolism, specifically demonstrating that the metabolic signature of an immune cell can instruct downstream effector function. Utilizing a combination of an in vitro model of tumor-conditioned human macrophages, an orthotopic pancreatic ductal adenocarcinoma mouse model and patient-derived specimens, we define a pronounced glycolytic signature in tumor-infiltrating myeloid cells that confer them a pro-tumoral phenotype. Inhibiting glycolysis with 2-deoxyglucose, macrophage-specific deletion of glucose transporter 1 or neutrophil-specific deletion of hypoxia-inducible factor 1-alpha independently ameliorates disease. Our results indicate that glycolysis is a key control point in the immunological reprogramming of tumor-infiltrating myeloid cells, and highlight the therapeutic potential of targeting this metabolic pathway to improve patient outcome.
DOI: 10.32657/10220/47516
Schools: School of Biological Sciences 
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Theses

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