Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function
Madhusudhanan Sukumar,Jie Liu,Yun Ji,Murugan Subramanian,Joseph G. Crompton,Zhiya Yu,Rahul Roychoudhuri,Douglas C. Palmer,Pawel Muranski,Edward D. Karoly,Robert P. Mohney,Christopher A. Klebanoff,Ashish Lal,Toren Finkel,Nicholas P. Restifo,Luca Gattinoni +15 more
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TLDR
It is indicated that augmenting glycolytic flux drives CD8+ T cells toward a terminally differentiated state, while its inhibition preserves the formation of long-lived memory CD8+, and the efficacy of T cell-based therapies against chronic infectious diseases and cancer.Abstract:
Naive CD8+ T cells rely upon oxidation of fatty acids as a primary source of energy. After antigen encounter, T cells shift to a glycolytic metabolism to sustain effector function. It is unclear, however, whether changes in glucose metabolism ultimately influence the ability of activated T cells to become long-lived memory cells. We used a fluorescent glucose analog, 2-NBDG, to quantify glucose uptake in activated CD8+ T cells. We found that cells exhibiting limited glucose incorporation had a molecular profile characteristic of memory precursor cells and an increased capacity to enter the memory pool compared with cells taking up high amounts of glucose. Accordingly, enforcing glycolytic metabolism by overexpressing the glycolytic enzyme phosphoglycerate mutase-1 severely impaired the ability of CD8+ T cells to form long-term memory. Conversely, activation of CD8+ T cells in the presence of an inhibitor of glycolysis, 2-deoxyglucose, enhanced the generation of memory cells and antitumor functionality. Our data indicate that augmenting glycolytic flux drives CD8+ T cells toward a terminally differentiated state, while its inhibition preserves the formation of long-lived memory CD8+ T cells. These results have important implications for improving the efficacy of T cell–based therapies against chronic infectious diseases and cancer.read more
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Natural Killer Cell Dysfunction in Obese Patients with Breast Cancer: A Review of a Triad and Its Implications.
Esraa Elaraby,Abdullah Imadeddin Malek,Hanan W. Abdullah,Noha Mousaad Elemam,Maha Saber-Ayad,Maha Saber-Ayad,Iman M. Talaat,Iman M. Talaat +7 more
TL;DR: In this paper, a triad of breast cancer, obesity, and natural killer cells (NK) dysfunction was investigated to elucidate a link between these pillars on a cellular level, which can help in designing a targeted immunotherapy with a low side effect profile that can revolutionize breast cancer treatment and improve survival in obese patients.
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Stem cell-like memory T cells: The generation and application
TL;DR: Stem cell-like memory T cells (Tscm) as discussed by the authors are a newly defined memory T cell subset with characteristics of long life span, consistent self-renewing, rapid differentiation into effector T cells, and apoptosis resistance.
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Metabolic changes and interaction of tumor cell, myeloid-derived suppressor cell and T cell in hypoxic microenvironment.
Xiantu Ou,Weibiao Lv +1 more
TL;DR: The effects of hypoxia on glucose metabolism of tumor cells, myeloid-derived suppressor cells and T cells in tumor microenvironment were reviewed, and the interaction among the three was also described.
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Nutrient Condition in the Microenvironment Determines Essential Metabolisms of CD8+ T Cells for Enhanced IFNγ Production by Metformin
Ruoyu Chao,Mikako Nishida,N. Yamashita,Miho Tokumasu,Weiyang Zhao,Ikuru Kudo,Heiichiro Udono +6 more
TL;DR: A direct effect of Met is revealed on IFNγ production of CD8+ T cells that was dependent on differential metabolic pathways and determined by nutrient conditions in the microenvironment and blocked by a mitochondrial ROS scavenger and not by an inhibitor of AMPK.
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The Na+/K+ ATPase Regulates Glycolysis and Defines Immunometabolism in Tumors
Sydney M. Sanderson,Zhengtao Xiao,Amy J. Wisdom,Shree Bose,Maria V. Liberti,Michael A. Reid,Emily Hocke,Simon G. Gregory,David G. Kirsch,Jason W. Locasale +9 more
TL;DR: In vivo and metabolomic results provide evidence that altering energy demands can be used to regulate glycolysis with cell-type specific consequences in a multicellular environment of biomedical interest.
References
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Journal ArticleDOI
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Ruoning Wang,Christopher P. Dillon,Lewis Zhichang Shi,Sandra Milasta,Robert Carter,David Finkelstein,Laura L. McCormick,Patrick Fitzgerald,Hongbo Chi,Joshua Munger,Douglas R. Green +10 more
TL;DR: Metabolic tracer analysis revealed a Myc-dependent metabolic pathway linking glutaminolysis to the biosynthesis of polyamines, which may represent a general mechanism for metabolic reprogramming under patho-physiological conditions.
Journal ArticleDOI
Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets
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TL;DR: Teff and Treg were selectively increased in Glut1 transgenic mice and reliant on glucose metabolism, whereas Treg had activated AMP-activated protein kinase and were dependent on lipid oxidation.