ArticleAlterationofTumorMetabolismbyCD4+TCellsLeadstoTNF-a-DependentIntensificationofOxidativeStressandTumorCellDeathGraphicalAbstractHighlightsdAdoptiveCD4+TcelltherapyinmiceinducesextensivemetabolicchangesintumordImmunotherapyleadstoglutathionedeficiencyandoxidativeDNAdamageintumordTNF-aandchemotherapysynergizetointensifyROSlevelsintumorviaNADPHoxidasedReducingtumoroxidativestressdiminishestheefficacyofadoptiveTcelltherapyAuthorsTsadikHabtetsion,Zhi-ChunDing,WenhuPi,...,BruceR.Blazar,DavidH.Munn,GangZhouCorrespondencegzhou@augusta.eduInBriefUsingapreclinicalmodelofcolorectaltumorstreatedwithCD4+Tcell-basedadoptiveimmunotherapy,Habtetsionetal.showthatprofoundmetabolicchangesoccurintumorsbeforetumorregression.TcellsshapetumormetabolismthroughTNF-a,whichcansynergizewithchemotherapy,toincreasetumorcelloxidativestressthroughanNOX-dependentmechanism.Habtetsionetal.,2018,CellMetabolism28,228–242August7,2018ª2018ElsevierInc.https://doi.org/10.1016/j.cmet.2018.05.012CellMetabolismArticleAlterationofTumorMetabolismbyCD4+TCellsLeadstoTNF-a-DependentIntensificationofOxidativeStressandTumorCellDeathTsadikHabtetsion,1,9,10Zhi-ChunDing,1,9WenhuPi,2TaoLi,3ChunwanLu,2TingtingChen,1CaixiaXi,1,4HelenaSpartz,5KebinLiu,2ZhonglinHao,1,6NahidMivechi,1,4YuqingHuo,7BruceR.Blazar,8DavidH.Munn,1andGangZhou1,6,11,*1GeorgiaCancerCenter,MedicalCollegeofGeorgia,AugustaUniversity,112015thStreet,CN-4140,Augusta,GA30912,USA2DepartmentofBiochemistryandMolecularBiology,MedicalCollegeofGeorgia,AugustaUniversity,Augusta,GA,USA3DepartmentofOncologyandSurgery,GeneralHospitalofNingxiaMedicalUniversity,804ShengliRoad,Yinchuan,NingxiaProvince750004,PRChina4MolecularChaperoneBiology,MedicalCollegeofGeorgia,AugustaUniversity,Augusta,GA,USA5DepartmentofPathology,SectionofAnatomicPathology,MedicalCollegeofGeorgia,AugustaUniversity,Augusta,GA,USA6DepartmentofMedicine,MedicalCollegeofGeorgia,AugustaUniversity,Augusta,GA,USA7VascularBiologyCenter,DepartmentofCellularBiologyandAnatomy,AugustaUniversity,August...
