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Immune glycolysis

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https://www.readbyqxmd.com/read/29156694/pdac-derived-exosomes-enrich-the-microenvironment-in-mdscs-in-a-smad4-dependent-manner-through-a-new-calcium-related-axis
#1
Daniela Basso, Elisa Gnatta, Andrea Padoan, Paola Fogar, Sara Furlanello, Ada Aita, Dania Bozzato, Carlo-Federico Zambon, Giorgio Arrigoni, Chiara Frasson, Cinzia Franchin, Stefania Moz, Thomas Brefort, Thomas Laufer, Filippo Navaglia, Sergio Pedrazzoli, Giuseppe Basso, Mario Plebani
Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4, deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4-dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3-SMAD4+) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29153034/advances-in-maldi-mass-spectrometry-within-drug-discovery
#2
Dale S Cornett, Michael D Scholle
Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain...
December 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29138369/-metabolic-competition-in-tumor-microenvironment
#3
Shingo Eikawa, Heiichiro Udono
Metabolic pathways tightly regulate T cell response in host defense against infection and cancer. Glycolysis plays a key role in effector T cell differentiation and its function. More recent studies have demonstrated that tumor microenvironment forms hypoxia and metabolic disadvantage of immune cells. These environmental attributions impair the effector T cell survival, proliferation and function. Therefore repurposing of metabolic drugs might develop a novel cancer immunotherapy based on the targeting of T cell immunometabolism...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29132538/immunometabolic-profiling-of-t-cells-from-patients-with-relapsing-remitting-multiple-sclerosis-reveals-an-impairment-in-glycolysis-and-mitochondrial-respiration
#4
Claudia La Rocca, Fortunata Carbone, Veronica De Rosa, Alessandra Colamatteo, Mario Galgani, Francesco Perna, Roberta Lanzillo, Vincenzo Brescia Morra, Giuseppe Orefice, Ilaria Cerillo, Ciro Florio, Giorgia Teresa Maniscalco, Marco Salvetti, Diego Centonze, Antonio Uccelli, Salvatore Longobardi, Andrea Visconti, Giuseppe Matarese
BACKGROUND: Metabolic reprogramming is shaped to support specific cell functions since cellular metabolism controls the final outcome of immune response. Multiple sclerosis (MS) is an autoimmune disease resulting from loss of immune tolerance against central nervous system (CNS) myelin. Metabolic alterations of T cells occurring during MS are not yet well understood and their studies could have relevance in the comprehension of the pathogenetic events leading to loss of immune tolerance to self and to develop novel therapeutic strategies aimed at limiting MS progression...
December 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29129693/foxj1-promotes-bladder-cancer-cell-growth-and-regulates-warburg-effect
#5
Shaozhong Xian, Donghao Shang, Guangqi Kong, Ye Tian
Forkhead Box J1 (FOXJ1) which belongs to Fox gene family, plays complex and crucial roles in processes of development, organogenesis, regulation of the immune system, as well as progression of several malignancies. However, how FOXJ1 functions in bladder cancer remains unclear. Here, we report that FOXJ1 is upregulated in most bladder cancer patients, and predicts poor clinical outcomes. FOXJ1 facilitates bladder cancer cell proliferation and colony formation. FOXJ1 knockdown suppresses bladder tumor growth in nude mice...
November 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29119048/elucidating-immunometabolic-targets-in-glioblastoma
#6
REVIEW
Pooja Agarwal, Michael J Pajor, David M Anson, Maheedhara R Guda, Collin M Labak, Andrew J Tsung, Kiran K Velpula
Immunometabolism has recently emerged on the forefront of cancer research as a new avenue to potentially develop more effective and targeted treatment options. Several pathologically altered metabolic targets across various cancer types have been identified, including lactate in aerobic glycolysis; tryptophan in amino acid metabolism; and arginine in the urea cycle. Numerous advancements have improved our understanding of the dual function of these targets in influencing immune functions as an auxiliary function to their well-established metabolic role...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29111350/metabolic-changes-in-tumor-cells-and-tumor-associated-macrophages-a-mutual-relationship
#7
Romana T Netea-Maier, Johannes W A Smit, Mihai G Netea
In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs)...
October 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29109698/the-emerging-facets-of-non-cancerous-warburg-effect
#8
Alyaa M Abdel-Haleem, Nathan E Lewis, Neema Jamshidi, Katsuhiko Mineta, Xin Gao, Takashi Gojobori
The Warburg effect (WE), or aerobic glycolysis, is commonly recognized as a hallmark of cancer and has been extensively studied for potential anti-cancer therapeutics development. Beyond cancer, the WE plays an important role in many other cell types involved in immunity, angiogenesis, pluripotency, and infection by pathogens (e.g., malaria). Here, we review the WE in non-cancerous context as a "hallmark of rapid proliferation." We observe that the WE operates in rapidly dividing cells in normal and pathological states that are triggered by internal and external cues...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29109251/metabolic-control-of-regulatory-t-cell-treg-survival-and-function-by-lkb1
#9
Nanhai He, Weiwei Fan, Brian Henriquez, Ruth T Yu, Annette R Atkins, Christopher Liddle, Ye Zheng, Michael Downes, Ronald M Evans
The metabolic programs of functionally distinct T cell subsets are tailored to their immunologic activities. While quiescent T cells use oxidative phosphorylation (OXPHOS) for energy production, and effector T cells (Teffs) rely on glycolysis for proliferation, the distinct metabolic features of regulatory T cells (Tregs) are less well established. Here we show that the metabolic sensor LKB1 is critical to maintain cellular metabolism and energy homeostasis in Tregs. Treg-specific deletion of Lkb1 in mice causes loss of Treg number and function, leading to a fatal, early-onset autoimmune disorder...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29109024/ampk-regulates-immunometabolism-in-sepsis
#10
Jun Huang, Ke Liu, Shan Zhu, Min Xie, Rui Kang, Lizhi Cao, Daolin Tang
Sepsis and septic shock remain challenging for intensive care units worldwide and have limited treatment options; therefore, identification of targetable key players in systemic inflammation and multiple organ failure is urgently needed. Here, we show that AMP-activated protein kinase (AMPK) is a negative regulator of bioenergetic reprogramming in immune cells and suppresses sepsis development in vivo. Mechanistically, AMPK deficiency increases pyruvate kinase isozyme M2 (PKM2)-dependent aerobic glycolysis, which leads to the release of high mobility group box 1 (HMGB1, a late mediator of lethal systemic inflammation) in macrophages and monocytes...
November 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29107106/the-role-of-nitric-oxide-in-metabolic-regulation-of-dendritic-cell-immune-function
#11
Phyu M Thwe, Eyal Amiel
Dendritic cells (DCs) are canonical antigen presenting cells of the immune system and serve as a bridge between innate and adaptive immune responses. When DCs are activated by a stimulus through toll-like receptors (TLRs), DCs undergo a process of maturation defined by cytokine & chemokine secretion, co-stimulatory molecule expression, antigen processing and presentation, and the ability to activate T cells. DC maturation is coupled with an increase in biosynthetic demand, which is fulfilled by a TLR-driven upregulation in glycolytic metabolism...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29107073/immunometabolic-determinants-of-chemoradiotherapy-response-and-survival-in-head-and-neck-squamous-cell-carcinoma
#12
Rosemarie Krupar, Matthias G Hautmann, Ravi R Pathak, Indu Varier, Cassandra McLaren, Doris Gaag, Claus Hellerbrand, Matthias Evert, Simon Laban, Christian Idel, Vlad Sandulache, Sven Perner, Anja K Bosserhoff, Andrew G Sikora
Tumor immune microenvironment and tumor metabolism are major determinants of chemoradiotherapy response. The interdependency and prognostic significance of specific immune and metabolic phenotypes in head and neck squamous cell carcinoma (HNSCC) were assessed and changes in reactive oxygen species were evaluated as a mechanism of treatment response in tumor spheroid/immunocyte co-cultures. Pretreatment tumor biopsies were immunohistochemically characterized in 73 HNSCC patients treated by definitive chemoradiotherapy and correlated with survival...
October 27, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29081778/pyruvate-kinase-m2-is-required-for-the-expression-of-the-immune-checkpoint-pd-l1-in-immune-cells-and-tumors
#13
Eva M Palsson-McDermott, Lydia Dyck, Zbigniew Zasłona, Deepthi Menon, Anne F McGettrick, Kingston H G Mills, Luke A O'Neill
Blocking interaction of the immune checkpoint receptor PD-1 with its ligand PD-L1 is associated with good clinical outcomes in a broad variety of malignancies. High levels of PD-L1 promote tumor growth by restraining CD8(+) T-cell responses against tumors. Limiting PD-L1 expression and function is therefore critical for allowing the development of antitumor immune responses and effective tumor clearance. Pyruvate kinase isoform M2 (PKM2) is also a key player in regulating cancer as well as immune responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29066174/attenuation-of-cd4-cd25-regulatory-t-cells-in-the-tumor-microenvironment-by-metformin-a-type-2-diabetes-drug
#14
Yuki Kunisada, Shingo Eikawa, Nahoko Tomonobu, Shohei Domae, Takenori Uehara, Shohei Hori, Yukihiro Furusawa, Koji Hase, Akira Sasaki, Heiichiro Udono
CD4(+)CD25(+) regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103(+)KLRG1(+) population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naïve CD4(+) T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1...
November 2017: EBioMedicine
https://www.readbyqxmd.com/read/29061801/a-simple-method-to-optimize-the-effectiveness-of-chemotherapy-modulation-of-glucose-intake-during-chemotherapy
#15
Philippe Icard, Bernard Teboul, Philip El Baze
BACKGROUND/AIM: Cancer cells consume high amounts of glucose to produce ATP and molecules entering biosynthesis. Numerous experimental studies have demonstrated that glucose deprivation and/or glycolysis inhibition arrest cancer cell growth and may increase the efficiency of cytotoxic drugs. In contrast, increasing glycolysis in tumor-infiltrating lymphocytes (TILs) activates these cells that destroy cancer cells. We propose to increase the efficiency of chemotherapy by modulating glucose intake during the course of chemotherapy...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29054873/the-enigmatic-genome-of-an-obligate-ancient-spiroplasma-symbiont-in-a-hadal-holothurian
#16
Li-Sheng He, Pei-Wei Zhang, Jiao-Mei Huang, Fang-Chao Zhu, Antoine Danchin, Yong Wang
Protective symbiosis has been reported in many organisms, but the molecular mechanisms of the mutualistic interactions between the symbionts and their host are unclear. Here, we sequenced the 424-Kbp genome of "Candidatus Spiroplasma holothuricola" that dominated the hindgut microbiome of a sea cucumber, a major scavenger captured in the Mariana trench (6140m depth). Phylogenetic relationships indicated that the dominant bacterium in the hindgut was derived from a basal group of Spiroplasma sp. In this organism, the genes responsible for biosynthesis of amino acids, glycolysis and sugar transporters were lost, strongly suggesting endosymbiosis...
October 20, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29047090/metabolic-reprogramming-and-redox-signaling-in-pulmonary-hypertension
#17
Lydie Plecitá-Hlavatá, Angelo D'alessandro, Karim El Kasmi, Min Li, Hui Zhang, Petr Ježek, Kurt R Stenmark
Pulmonary hypertension is a complex disease of the pulmonary vasculature, which in severe cases terminates in right heart failure. Complex remodeling of pulmonary arteries comprises the central issue of its pathology. This includes extensive proliferation, apoptotic resistance and inflammation. As such, the molecular and cellular features of pulmonary hypertension resemble hallmark characteristics of cancer cell behavior. The vascular remodeling derives from significant metabolic changes in resident cells, which we describe in detail...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29032101/mitochondrial-activity-in-t-cells
#18
REVIEW
Gabriela Desdín-Micó, Gonzalo Soto-Heredero, María Mittelbrunn
Mitochondria fulfill important and diverse roles during the different stages of T cell adaptive responses. Here we discuss the role of the mitochondria in T cells from the initial steps of activation at the immune synapse to their participation in memory responses and T cell exhaustion. Mitochondria are relocated to the immune synapse in order to supply local ATP and to aid calcium signaling. During expansion and proliferation, mitochondrial reactive oxygen species drive proliferation. Aerobic glycolysis, glutaminolysis and fatty acid oxidation regulate the program of differentiation into effector or regulatory T cell subsets, and mitochondrial remodeling proteins are required for the long-lasting phenotype of memory cells...
October 12, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29030115/store-operated-ca-2-entry-controls-clonal-expansion-of-t-cells-through-metabolic-reprogramming
#19
Martin Vaeth, Mate Maus, Stefan Klein-Hessling, Elizaveta Freinkman, Jun Yang, Miriam Eckstein, Scott Cameron, Stuart E Turvey, Edgar Serfling, Friederike Berberich-Siebelt, Richard Possemato, Stefan Feske
Store-operated Ca(2+) entry (SOCE) is the main Ca(2+) influx pathway in lymphocytes and is essential for T cell function and adaptive immunity. SOCE is mediated by Ca(2+) release-activated Ca(2+) (CRAC) channels that are activated by stromal interaction molecule (STIM) 1 and STIM2. SOCE regulates many Ca(2+)-dependent signaling molecules, including calcineurin, and inhibition of SOCE or calcineurin impairs antigen-dependent T cell proliferation. We here report that SOCE and calcineurin regulate cell cycle entry of quiescent T cells by controlling glycolysis and oxidative phosphorylation...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29027371/differential-proteomic-analysis-of-dimethylnitrosamine-dmn-induced-liver-fibrosis
#20
Xiujie Liu, Rongji Dai, Ming Ke, Imran Suheryani, Weiwei Meng, Yulin Deng
Liver fibrosis is a common pathological feature of many chronic liver diseases. To characterize the entire panorama of proteome changes in DMN-induced liver fibrosis, iTRAQ-based differential proteomic analysis was performed with DMN-induced liver fibrosis rats. A total of 4155 confidently identified proteins were found, with 365 proteins showing significant changes (fold changes of >1.5 or < 0.67, P < 0.05). In metabolic activation, proteins assigned to drug metabolism enzymes (e.g., CYP2D1) changed, suggesting that the liver protection mechanism was activated to relieve DMN toxicity...
October 13, 2017: Proteomics
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