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Epigenetic reprogramming of CD4(+) Helper T cells as a strategy to improve anticancer immunotherapy

Cysteine is rate-limiting for glutathione synthesis in cells under oxidative stress

Abbreviations CSCs: Cancer stem cells CTLA-4: Cytotoxic T lymphocyte-associated antigen 4 PD-1: Programmed Cell Death Protein 1 PD-L1: Programmed Death Ligand 1 NSCLC: Non-small-cell lung cancer MDR: Multi-drug resistant HCC: Hepatocellular carcinoma DTP: Drug-tolerant persister DNMTs: DNA Methyltransferases DNAm: DNA methylation 5-FU: 5-Fluorouracil P-gp: P-glycoprotein Bcl-2: B-cell lymphoma 2 Bcl-xl: B-cell lymphoma-extra large IAPs: Inhibitors of apoptosis Bid: BH3 interacting-domain death agonist Bax: Bcl-2 Associated X-protein Bim: Bcl-2 Interacting Mediator of cell death PUMA: P53 upregulated modulator of apoptosis CRC: Colorectal carcinoma DOX: Doxorubicin MAPK: Mitogen-activated protein kinase KMTs: Histone lysine methyltransferase PRMTs: Protein arginine methyl transferase GSH: Glutathione DNA-PK: DNA-dependent protein kinase SASP: Senescence-associated secretory phenotype AML: Acute myeloid leukemia Notch 1: Neurogenic locus notch homolog protein 1 Wnt: Wingless-related integration site TGF-: Transforming growth factor- ESCs: Embryonic stem cells SOX2: Sex determining region Y-box 2 OCT4: Octamer-binding transcription factor 4 KLF4: Kruppel-like factor 4 SALL4: Sal-like protein 4 FOXM1: Forkhead box protein M1 Hh: Hedgehog Chk: Checkpoint kinase UBC: Urothelial bladder cancer EMT: Epithelial-to-mesenchymal transition MET: Mesenchymal-to-epithelial transition TNBC: Triple-negative breast cancer ABCG: ATP binding cassette subfamily G FBXO21: F-Box Protein 21 GSTp: Glutathione S-transferase p uPA: Urokinase Plasminogen Activator HIF-1: Hypoxia Inducible factor-1 CRISPR/Cas9: Clustered regularly interspaced short palindromic repeats/ Caspase 9 ATG: Autophagy-related ROS: Reactive oxygen species ALDH: Aldehyde dehydrogenase TNBCSC: Triple-negative breast cancer stem cells JAK/STAT: Janus Kinase/signal transducers and activators of transcription IL: Interleukin CCL2: CC-Chemokine ligand 2 CSF1: Colony stimulating factor 1 CSF2: Colony stimulating factor 2 HGF: Hepatocyte growth factor MIF: Macrophage migration inhibitory factor CX3CL1: C-X3-C motif Chemokine ligand 1 PGE2: Prostaglandin E2 SDF-1: Stromal cell-derived factor 1 LOX: Lysyl oxidase CCL3: CC-Chemokine ligand 3 CCL5: CC Chemokine ligand 5 VEGF-A: Vascular endothelial growth factor A PTN: Pleiotrophin HMGB1: High-mobility group box 1 TAMs: Tumor-associated macrophages EGFR: Epidermal growth factor receptor IDO1: Indoleamine 2,3-dioxygenase 1 PGE: Prostaglandin ENTPD2: Ectonucleoside triphosphate diphosphohydrolase 2 CD: Clusters of differentiation MDSC: Myeloid-derived suppressor cells CAR T cell: Chimeric antigen receptor T cell CRS: Cytokine release syndrome ZEB1: Zinc finger E-box binding homeobox 1 HDAC: Histone deacetylase ATM: Ataxia-telangiectasia mutated PCAF: p300/CBP-associated factor FBXW7: F-box and WD repeat domain-containing 7 TWIST1: Twist-related protein 1 OXPHOS: Oxidative phosphorylation LMP: Lysosomal membrane permeability UCP2: Uncoupler protein 2 mTOR: Mammalian target of rapamycin NF-B: Nuclear factor- B STAT3: Signal transducer and activator of transcription3 MRP: Multidrug resistance protein TRAIL: Tumor related apoptosis-inducing ligand GBM: Glioblastoma multiforme VIM: Vimentin VDAC: Voltage-dependent anion channel OHCP: 4-Hydroxy-cyclophosphamide OATPs: Organic anion-transporting polypeptides LRP: Lung resistance-related protein UPR: Unfolded protein response LC3: Light chain 3 CML: Chronic myelogenic leukemia cells (CML) JNK: Jun N-terminal kinase DUSP4: Dual specificity protein phosphatase 4 ERK: Extracellular signal-regulated kinase ATF4: Activating transcription factor 4 ZNF143: Zinc-finger factor 143 YB-1: Y-box binding protein-1 BUB1: Budding uninhibited by benzimidazoles 1 CCNB1: Cyclin B1 CENPE: Centromere protein E CENPF: Centromere protein F References Nikolaou M, et al

doi:10.1080/14656566.2019.1615057

Before treatment, numbing cream is applied for comfort