简介：Cisplatinandotherplatinum-baseddrugsareusedfrequentlyfortreatmentoflungcancer.However,theirclinicalperformanceareusuallylimitedbydrugresistanceortoxiceffects.Carnosicacid,apolyphenolicditerpeneisolatedfromRosemary(Rosemarinusofficinalis),hasbeenreportedtohaveseveralpharmacologicalandbiologicalactivities.Inthepresentstudy,thecombinationeffectofcisplatinpluscarnosicacidonmouseLLC(Lewislungcancer)xenograftsandpossibleunderlyingmechanismofactionwereexamined.LLC-bearingmiceweretreatedwithintraperitonealinjectionwithcisplatin,oralgavagewithcarnosicacid,orcombinationwithcisplatinandcarnosicacid,respectively.Combinationofcarnosicacidandcisplatinyieldedsignificantlybetteranti-growthandpro-apoptoticeffectsonLLCxenograftsthandrugsalone.MechanisticstudyshowedthatcarnosicacidtreatmentboostedthefunctionofCD8~+TcellsasevidencedbyhigherIFN-γsecretionandhigherexpressionofFasL,perforinaswellasgranzymeB.Inthemeantime,theproportionofMDSC(myeloid-derivedsuppressorcells)intumortissueswerereducedbycarnosicacidtreatmentandthemRNAlevelsofiNOS2,Arg-1,andMMP9,whicharethefunctionalmarkersforMDSC,werereduced.Inconclusion,ourstudyprovedthatthefunctionalsuppressionofMDSCbycarnosicacidpromotedthelethalityofCD8~+Tcells,whichcontributedtotheenhancementofanti-lungcancereffectofcisplatin.