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Paper Reading Impaired enolase 1 glycolytic activity restrains effector functions of tumor-infiltrating CD8+ T cells  Lelisa F. Gemta et al Science Immunology The tumor microenvironment can promote tumor infiltrating CD8+ T cells exhaustion. Metabolic manipulation has been proved essential in regulating T cell function. Here the authors characterized that CD8+ TILs showed lower glycolytic activity than acute Teff but more active than naïve CD8+ T cells. They first checked the glucose availability and found the glucose uptake was not impaired in CD8+ TILs and the canonical signaling pathways did not change a lot as well. They further turned to the metabolomics analysis and found some clue. The metabolomics data showed PEP deficiency in CD8+ TILs. Enolase 1 is a critical enzyme for PEP production in glycolysis. Next, the authors demonstrated that glycolytic metabolism was restrained by enolase 1 activity rather than expression level, implying that enolase function was regulated at the posttranslational level in CD8+ TILs. They further added exogenous PEP and pyruvate to bypass enolase inactivity and rescued glycolysis and OXPHOS metabolism as well as effector function of CD8 TILs. Finally, the authors linked their finding to the clinical therapy and found the checkpoint signals contributed to the low enolase activity and human melanoma CD8+ TILs also showed lower enolase activity. This paper put forward that restoration of enolase 1 activity might be expected to revert the anti-tumor function of CD8 T cells. http://immunology./content/4/31/eaap9520 A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development  Yannick Boege et al. Cancer Cell Hepatocyte apoptosis plays dual role in liver homeostasis. On the one hand, it protects liver by eliminating damaged hepatocytes. On the other hand, chronically increased hepatocyte apoptosis is harmful. Here the authors functionally and quantitatively examine the interplay between caspase-8-dependent hepatocyte apoptosis and regeneration-associated replication stress, genetic instability and hepatocarcinogenesis and showed that persistently increased levels of hepatocyte apoptosis tightly correlated with subsequent HCC development. Dissecting the role of caspase-8 for hepatocyte apoptosis, the authors discovered a non-apoptotic function of caspase-8 in sensing DNA damage and H2AX phosphorylation. https://www./science/article/pii/S1535610817303549?via%3Dihub Edited by Biaolong Deng |
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