Objective:MemorystemTcells(Tscm)haveattractedattentionbecauseoftheirenhancedself-renewal,multipotentcapacity,andanti-tumorcapacities.However,littleisknownaboutTscminpatientswithrenalclearcellcarcinoma(RCC)andtheroleofWntsignalinginthesecells.WeevaluatedTscmfromRCCpatientsconcerningtheiractivationofWntsignalinginvitroandexploredthemechanismofpreferentialsurvival.Methods:FlowcytometryidentifiedsurfacemarkersandcytokinesproducedfromaccumulatedTscminthepresenceoftheglycogensynthasekinasebetainhibitorTWS119.Apoptosiswasevaluatedafterinductionusingtumornecrosisfactor-alpha.ImmunofluorescenceandWesternblotanalyseswereusedtoinvestigatetheactivationofthenuclearfactor-kappaB(NF-КB)pathway.Results:RCCpatientshadasimilarpercentageofCD4~+andCD8~+Tscmashealthydonors.ActivationofWntsignalingbyTWS119resultedintheaccumulationofTscminactivatedTcells,butreversalofdifferentiatedTcellstoTscmwasnotachieved.PreferentialsurvivalofTscmwasassociatedwithincreasedanti-apoptoticabilitymediateddownstreamoftheNF-КBactivationpathway.Conclusions:ThefindingthatTscmcanaccumulatebyWntsignalinginvitroinbloodfromRCCpatientswillhelpindevisingnewcancertherapystrategiesofTscm-basedadoptiveimmunotherapy,suchasdendriticcell-stimulatedTscm,andTcellreceptororchimericantigenreceptor-engineeredTscm.
