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were investigators in trials included in this analysis (STEP 1: J.P.H.W., STEP 3: J.P.F

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Food and Drug Administration GAPDH: Glyceraldehyde-3-phosphate dehydrogenase GLUT1: Glucose transporter protein 1 GPX: Glutathione peroxidase H 2 O 2 : Hydrogen peroxide HIF-1: Hypoxia-inducible factor-1 alpha HMTs: Histone methyltransferases HDACs: Histone deacetylases iNOS: Inducible nitric oxide synthase IDH2: Isocitrate dehydrogenase 2 ICIs: Immune checkpoint inhibitors ITIM: Immunoreceptor tyrosine inhibitory motif ITSM: Immunoreceptor tyrosine switch motif KMTi: Lysine methyltransferase inhibitors LKB1: Liver-associated kinase B1 LDH: Lactate dehydrogenase MSCs: Mesenchymal stem cells MDSCs: Myeloid-derived suppressor cells MnSOD: Manganese superoxide dismutase mROS: Mitochondrial ROS mTOR: Mammalian target of rapamycin MMP: Mitochondrial membrane potential mtDNA: Mitochondrial DNA MitoQ: Mitoquinone NAC: N-acetylcysteine NRF-1: Nuclear respiratory factor 1 NAD + : Nicotinamide adenine dinucleotide NR: Nicotinamide riboside NOX: NADPH oxidase NAM: Niacinamide NSCLC: Non-small cell lung cancer NFAT: Nuclear factor of activated T cells NF-B: Nuclear factor kappa B O 2 : Superoxide anions OH: Hydroxyl radicals Opa1: Optic atrophy 1 OXPHOS: Oxidative phosphorylation PFKL: Phosphofructokinase PGC-1: PPAR coactivator-1-alpha PI3K: Phosphatidylinositol 3-kinase PKM: Pyruvate kinase M PGK1: Phosphoglycerate kinase 1 ROS: Reactive oxygen species SHP-1: Src homology phosphatase 1 SHP-2: Src homology phosphatase 2 scFv: Single-chain variable fragment TCA: Tricarboxylic acid TCR: T cell receptor TILs: Tumor-infiltrating lymphocytes TME: Tumor microenvironment TFAM: Mitochondrial transcription factor A T m : Memory CD8 + T cells T pex : Precursor exhausted T cells T regs : Regulatory T cells T scm : Stem cell-like memory T cells T eff : Effector T cells T ex : Exhausted T cells TAMs: Tumor-associated macrophages References Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O, et al