26 research outputs found

    The Sweet Surrender: How Myeloid Cell Metabolic Plasticity Shapes the Tumor Microenvironment

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    Immune cells are one of the most versatile cell types, as they can tailor their metabolic activity according to their required function. In response to diverse environmental cues, immune cells undergo metabolic reprogramming to support their differentiation, proliferation and pro-inflammatory effector functions. To meet a dramatic surge in energetic demand, immune cells rewire their metabolism to utilize aerobic glycolysis. This preferential use of glycolysis even under aerobic conditions is well established in tumor cells, and is known as the “Warburg effect.” Tumor cells avidly use glucose for aerobic glycolysis, thereby creating a nutrient-starved microenvironment, outcompeting T cells for glucose, and directly inhibiting T-cell anti-tumoral effector function. Given that both immune and tumor cells use similar modes of metabolism in the tumor stroma, it is imperative to identify a therapeutic window in which immune-cell and tumor-cell glycolysis can be specifically targeted. In this review, we focus on the Warburg metabolism as well as other metabolic pathways of myeloid cells, which comprise a notable niche in the tumor environment and promote the growth and metastasis of malignant tumors. We examine how differential immune-cell activation triggers metabolic fate, and detail how this forbidding microenvironment succeeds in shutting down the vigorous anti-tumoral response. Finally, we highlight emerging therapeutic concepts that aim to target immune-cell metabolism. Improving our understanding of immunometabolism and immune-cell commitment to specific metabolic fates will help identify alternative therapeutic approaches to battle this intractable disease

    ENGINEERING PROBIOTICS TO MODULATE IMMUNE RESPONSES AGAINST BLADDER CARCINOMA

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    Ph.DDOCTOR OF PHILOSOPHY (NUSGS

    Metabolic reprogramming of tumor-infiltrating myeloid cells conveys protection against pancreatic ductal adenocarcinoma

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    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.Doctor of Philosoph

    UNCERTAINTY: NUDGING SELF-SERVICE TECHNOLOGY USAGE IN SUPERMARKETS THROUGH INDUCED UNCERTAIN WAIT TIME

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    Bachelor'sBachelor of Business Administration (Honours

    Targeting immune cells for cancer therapy

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    10.1016/j.redox.2019.101174Redox Biology2510117

    Green supply chain management: impact on environmental performance and firm competitiveness

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    Unrestrained industrialisation resulting in environmental pollution has mobilised the unstinting endeavours of scientist, researchers, policy makers and ecologist in a quest to rapidly unearth solutions to mitigate further environmental deterioration. One promising ongoing development is green supply chain management (GSCM), which promises a reduction of pollution and waste in manufacturing. GSCM achieves this through the mechanism of improving manufacturing efficiency, by reducing costs, enhancing product quality and improving product delivery. This study applies the natural resource-based view, and quantitatively examines the impact of the implementation of GSCM on firm environmental performance, and firm competitiveness. Data was collected from 122 sampled firms, analysed, and evaluated in two ways. Firstly, using partial least squared-structured equation modelling (PLS-SEM), results indicate that ‘green procurement’, and ‘green supplier and customer collaboration’, have a significant positive relationship with both firm environmental performance, and, firm competitiveness. Secondly, using importance-performance matrix analysis (IPMA), both ‘green procurement’ and ‘green supplier and customer collaboration’ are mapped in the high in importance/high-performance quadrant. The practical recommendations are for organisations to prioritise efforts and resources towards ‘green procurement’ and ‘green supplier and customer collaboration’ in order to maximise the return on ‘green’ investmen
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