Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function.

By Madhusudhanan Sukumar, Jie Liu, Yun Ji, Murugan Subramanian, Joseph G Crompton, Zhiya Yu, R. Roychoudhuri, D. Palmer, P. Muranski, Edward D. Karoly and 6 more. Journal of Clinical Investigation, 2013

897 citations recorded by the source corpus.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/afde7d4fde74ead099c0aa2c24e1ea4014a80e31

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Citations in the corpus

Metabolic Instruction of Immunity (2017, positive): “Repurposing the knowledge gained from such studies, boosting oxidative capacity and efficiency through enforcement of mitochondrial fusion or dampening glycolysis with 2-DG, extends the survival and antitumor function of CD8 T cells in models of adoptive cell therapy (Buck et al., 2016; Sukumar et a”
Foxp3 reprograms T cell metabolism to function in low glucose high lactate environments (2017, methodology): “Glucose Uptake by Flow Cytometry Formeasuring glucoseuptake inT cells,weused2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose, purchased from Cayman Chemicals), based upon a previously published protocol (Sukumar et al., 2013).”
Regulation of glycolysis by the hypoxia‐inducible factor (HIF): implications for cellular physiology (2020, background): “…include those which are inflamed, infected or tumour burdened, where hypoxia is common place, as well as those tissues which experience persistent low levels of oxygenation (so called ‘physiological hypoxia’), such as the bone marrow, placenta or gastrointestinal tract (Taylor & Colgan, 2017).”
L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity (2016, background): “, 2005), which in T cells may enhance memory T cell formation and anti-tumor responses (Sukumar et al., 2013), we considered a direct effect of L-arginine on protein functions.”
A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small cell lung cancer treated with PD-1 blockade (2018, neutral): “5 (2D1), -CD56 PE (CMSSB), - CD3 APC-eFluor780 (SK7), -Lag-3 FITC (3DS223H), -TIGIT PE (MBSA43), -2B4 FITC (eBioDM244), -CD137 FITC (4B4), -IL-2 PE (MQ1-17H12), -TNF-α APC (MAb11), - CD26 FITC (2A6), -CXCR5 Biotin (MU5UBEE), -ICOS FITC (ISA-3), -CD38 APC (HIT2), -Eomes eFluor660 (WD1928), -T-bet PE ”
Mitochondria in the regulation of innate and adaptive immunity (2015, positive): “Further evidence supporting the importance of mitochondrial metabolism comes from the observation that increasing or decreasing glycolytic flux, which reciprocally modulates mitochondrial metabolism, results in enhanced or diminished generation of memory T cells, respectively (Sukumar et al., 2013).”
The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo. (2015, result): “Both CD8 and CD4 T cells demonstrated a sharp decline in ECAR while increasing their OCR:ECAR ratio under glucose-free conditions (Figures 1H and 1I and S1D and S1E), consistent with previous results (Chang et al., 2013; Sukumar et al., 2013).”
Memory CD8+ T cells use cell intrinsic lipolysis to support the metabolic programming necessary for development (2014, background): “…with a recent paper showing that restraining terminal differentiation of Teff cells in vitro by treating with the glycolysis inhibitor 2-DG forms better memory T cells in vivo (Sukumar et al., 2013), because 2-DG was administered in the Teff phase, but not during memory T cell development.”
Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy. (2020, background): “…cell proliferation and has been shown to support the formation of long term memory CD8+ T cells, but can also suppress the proliferation and function of tumor infiltrating effector immune cells (Bonuccelli et al., 2010; Kouidhi, Ayed, & Elgaaied, 2018; Sukumar et al., 2013; D. Zhang et al., 2014).”
Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions (2015, methodology): “support of these data, we treated CD4 or CD8 T cells with the fluorescent analogues of glucose, 6-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (6-NBDG), and 2-(N(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG), in the presence or absence of sodium lactate or lactic ac”