mTOR inhibition potentiates cytotoxicity of Vγ4 γδ T cells via up‐regulating NKG2D and TNF‐α

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: rapamycin;    cytotoxicity;    STAT5;   

DOI  :  10.1189/jlb.5A0116-053RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

γδTcellsplayacriticalroleinearlyanti‐tumorimmunityandperformcytotoxicityviaNKG2Dforrecognitionandmultiplecytotoxicfactorsfortumorkilling.RecentstudieshavedemonstratedpivotalrolesofmTOR‐mediatedmetabolisminthematuration,differentiation,andeffectorfunctionofdiverseimmunecells,includingDCs,NKcells,CD4+Tcellsubsets,andCD8+Tcells,buttheroleofmTORsignalinginγδTcellsisbarelyknown.Here,weshowedthatsuppressingmTORsignalingininvitro‐expandedVγ4γδTcellsviathemechanisticinhibitorrapamycinenhancedtheircytotoxicityagainstmultipletumorcelllines,andthesecellsperformedbettertumor‐suppressingeffectsuponadoptivetherapy.Furtherinvestigationrevealedthatelevatedcytotoxicitywasaresultofup‐regulationofNKG2DandTNF‐α.Moreover,rapamycintreatmentsignificantlydecreasedtheexpressionofCISHandincreasedpSTAT5.TheinhibitionofSTAT5pathwaysviasiRNAinterferenceoraspecificinhibitoreliminatedtheup‐regulationofNKG2DandTNF‐αinrapamycin‐treatedVγ4γδTcells.TheseresultsuncoveredanimportantroleofmTORsignalinginthecytotoxiceffectorfunctionofγδTcellsandprovidedapotentialstrategytoimproveγδTcell‐basedcancerimmunotherapy...

【 授权许可】

CC BY