TumorandMicroenvironmentEvolutionduringImmunotherapywithNivolumabNadeemRiaz1,2,3,*,JonathanJ.Havel1,*,VladimirMakarov1,3,*,AlexisDesrichard1,*,WalterJ.Urba4,JenniferS.Sims1,3,F.StephenHodi5,SalvadorMartín-Algarra6,RajarsiMandal7,WilliamH.Sharfman8,ShailenderBhatia9,Wen-JenHwu10,ThomasF.Gajewski11,CraigL.SlingluffJr.12,DiegoChowell1,3,SviatoslavM.Kendall1,3,HanChang13,RachnaShah1,FengshenKuo3,LucG.T.Morris3,7,John-WilliamSidhom14,JonathanP.Schneck14,ChristineE.Horak13,NilsWeinhold2,‡,andTimothyA.Chan1,2,3,‡1HumanOncologyandPathogenesisProgram,MemorialSloanKetteringCancerCenter,NewYork,NY10065,USA2Dept.ofRadiationOncology,MemorialSloanKetteringCancerCenter,NewYork,NY10065,USA3ImmunogenomicsandPrecisionOncologyPlatform,MemorialSloanKetteringCancerCenter,NewYork,NY10065,USA4EarleA.ChilesResearchInstitute,ProvidenceCancerCenter,Portland,OR97213,USA5Dept.ofMedicalOncology,Dana-FarberCancerInstitute,Boston,MA02215,USA6MedicalOncology,ClínicaUniversidaddeNavarra,InstitutodeInvestigaciónSanitariadeNavarra,31008Pamplona,Spain7Dept.ofSurgery,MemorialSloanKetteringCancerCenter,NewYork,NY10065,USA8SidneyKimmelComprehensiveCancerCenter,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,MD21287,USA9FredHutchinsonCancerResearchCenter,UniversityofWashington,Seattle,WA98105,USA10Dept.ofMelanomaMedicalOncology,UniversityofTexasMDAndersonCancerCenter,Houston,TX77030,USA‡Correspondence:chant@mskcc.org(T.A.C.,leadcontact),weinholn@mskcc.org(N.W.).*Theseauthorscontributedequallytothiswork.AUTHORCONTRIBUTIONSFundingacquisition:T.A.C.Conceptualization:T.A.C.,N.R.,C.E.H.,andW.J.U.Clinicaltrialimplementationandaccrual:W.J.U.,F.S.H.,S.M-A.,W.H.S.,S.B.,W-J.H.,T.F.G.,C.L.S.,andC.E.H.Investigationandformalanalysis:N.R.,V.M.,andS.M.K.Analysisofpre-andon-therapychangesinmutationloadandclonality:N.W.,V.M.,andN.R.Neoantigenanalysis:D.C.,V.M.,N.R.,andJ.J.H.AnalysisofRNA-seqdata:A.D.,F.K.,H.C.,R.M.,andN.R.Exome-seqdatafrompre-therapysamples:V.M.,L.G.T.M.,andN.R.AnalysisofTCR-seqdata:J.J.H.,J.S.S...
