10 research outputs found
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PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation
During activation, T cells undergo metabolic reprogramming, which imprints distinct functional fates. We determined that on PD-1 ligation, activated T cells are unable to engage in glycolysis or amino acid metabolism but have an increased rate of fatty acid β-oxidation (FAO). PD-1 promotes FAO of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase ATGL, the lipolysis marker glycerol and release of fatty acids. Conversely, CTLA-4 inhibits glycolysis without augmenting FAO, suggesting that CTLA-4 sustains the metabolic profile of non-activated cells. Because T cells utilize glycolysis during differentiation to effectors, our findings reveal a metabolic mechanism responsible for PD-1-mediated blockade of T-effector cell differentiation. The enhancement of FAO provides a mechanistic explanation for the longevity of T cells receiving PD-1 signals in patients with chronic infections and cancer, and for their capacity to be reinvigorated by PD-1 blockade
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Clinical significance of T cell metabolic reprogramming in cancer
Conversion of normal cells to cancer is accompanied with changes in their metabolism. During this conversion, cell metabolism undergoes a shift from oxidative phosphorylation to aerobic glycolysis, also known as Warburg effect, which is a hallmark for cancer cell metabolism. In cancer cells, glycolysis functions in parallel with the TCA cycle and other metabolic pathways to enhance biosynthetic processes and thus support proliferation and growth. Similar metabolic features are observed in T cells during activation but, in contrast to cancer, metabolic transitions in T cells are part of a physiological process. Currently, there is intense interest in understanding the cause and effect relationship between metabolic reprogramming and T cell differentiation. After the recent success of cancer immunotherapy, the crosstalk between immune system and cancer has come to the forefront of clinical and basic research. One of the key goals is to delineate how metabolic alterations of cancer influence metabolism-regulated function and differentiation of tumor resident T cells and how such effects might be altered by immunotherapy. Here, we review the unique metabolic features of cancer, the implications of cancer metabolism on T cell metabolic reprogramming during antigen encounters, and the translational prospective of harnessing metabolism in cancer and T cells for cancer therapy
Rate-Limiting Mass Transfer in Micropollutant Degradation Revealed by Isotope Fractionation in Chemostat
International Comparative Analysis for Energy Efficiency of Transport Sectors in OECD Countries - Using Energy Intensity Method and Malmquist Approach -
Market Structure and Technical Efficiency in the Hospital Services Industry: A DEA Approach
O-Acetylation of Sialic Acids is Required for the Survival of Lymphoblasts in Childhood Acute Lymphoblastic leukemia (ALL)
Exploiting the selective affinity of Achatinin-H
towards 9-O-acetylneuraminic acid(α2-6)GalNAc, we have
demonstrated the presence of 9-O-acetylated sialoglycoproteins
(Neu5,9Ac2-GPs) on hematopoietic cells of children
suffering from acute lymphoblastic leukemia (ALL), indicative
of defective sialylation associated with this disease.
The carbohydrate epitope of Neu5,9Ac2-GPsALL was
confirmed by using several synthetic sialic acid analogues.
They are functionally active signaling molecules as demonstrated
by their role in mediating lymphoproliferative
responses and consequential increased production of IFN-γ
due to specific stimulation of Neu5,9Ac2-GPs on
PBMCALL with Achatinin-H. Cells devoid of 9-Oacetylations
(9-O-AcSA−) revealed decreased nitric oxide
production as compared to 9-O-AcSA+ cells on exposure to
IFN-γ. Under this condition, a decrease in viability of 9-OAcSA−
cells as compared to 9-O-AcSA+ cells was also
observed which was reflected from increased caspase 3
activity and apoptosis suggesting the protective role of this
glycotope
Explaining the efficiency of local health departments in the U.S.: an exploratory analysis
Public health, Efficiency, Data envelopment analysis,