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Article
Open AccessPyruvate dehydrogenase operates as an intramolecular nitroxyl generator during macrophage metabolic reprogramming
M1 macrophages enter a glycolytic state when endogenous nitric oxide (NO) reprograms mitochondrial metabolism by limiting aconitase 2 and pyruvate dehydrogenase (PDH) activity. Here, we provide evidence that N...
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Article
Open AccessItaconic acid underpins hepatocyte lipid metabolism in non-alcoholic fatty liver disease in male mice
Itaconate, the product of the decarboxylation of cis-aconitate, regulates numerous biological processes. We and others have revealed itaconate as a regulator of fatty acid β-oxidation, generation of mitochondrial...
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Article
The promise and peril of targeting cell metabolism for cancer therapy
A major challenge of cancer immunotherapy is the potential for undesirable effects on bystander cells and tumor-associated immune cells. Fundamentally, we need to understand what effect targeting tumor metabol...
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Article
Open AccessTumour-elicited neutrophils engage mitochondrial metabolism to circumvent nutrient limitations and maintain immune suppression
Neutrophils are a vital component of immune protection, yet in cancer they may promote tumour progression, partly by generating reactive oxygen species (ROS) that disrupts lymphocyte functions. Metabolically, ...
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Article
Open AccessROCK2, but not ROCK1 interacts with phosphorylated STAT3 and co-occupies TH17/TFH gene promoters in TH17-activated human T cells
Rho-associated coiled-coil kinase (ROCK)2 targeting down-regulates autoimmune responses in animal models and patients, however the underlying molecular mechanism is still an enigma. We report that ROCK2 binds ...
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Article
Killer immunoglobulin-like receptor (KIR) and KIR–ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2
NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR–ligand interactions. Inhibitory KIR–ligands have been identified ...
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Article
Open AccessCD40 expression in renal cell carcinoma correlates with tumor apoptosis, CD8 T cell frequency and patient survival
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Article
Open AccessHepatic myeloid-derived suppressor cells in tumor bearing mice exacerbate hepatitis and transform into pro-inflammatory myeloid cells
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The Role of Myeloid Derived Suppressor Cells in Cancer
Inflammation is established as one of the central hallmarks of cancer. Although the immune system plays an indispensable role in immunosurveillance against cellular transformation, ample evidence demonstrates ...
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Article
IFN-γ mediates CD4+ T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy
Protective cell-mediated immune responses in cancer are critically dependent on T-helper type 1 (TH1) cytokines such as interferon-γ (IFN-γ). We have previously shown that the combination of CD40 stimulation and ...
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Article
Rapid, in vivo, evaluation of antiangiogenic and antineoplastic gene products by nonviral transfection of tumor cells
Using a nonviral, electroporation-based gene transfection approach, we demonstrate the efficient and consistent transfection of two poorly immunogenic tumor cell lines: B16F10 melanoma and renal carcinoma (REN...
