At the Bench: Preclinical rationale for exploiting NK cells and γδ T lymphocytes for the treatment of high‐risk leukemias

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

关键词: blood cancer;    hematopoietic stem cell transplantation;    haploidentical;    cytomegalovirus;   

DOI  :  10.1189/jlb.0613312

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

NKcellsandγδTlymphocytesdisplaypotentcytolyticactivityagainstleukemiasandCMV‐infectedcellsandarethus,promisingimmuneeffectorcellsinthecontextofallo‐HSCT.NKcellsexpressHLAclassI‐specificinhibitoryreceptorsandpreferentiallykillHLAclassIlowtumorsorvirus‐infectedcells.KillingoccursuponengagementofactivatingNKRswithligandsthatareup‐regulatedontumorsandinfectedcells.Asimilaractivatingreceptor/ligandinteractionstrategyisusedbyγδTcells,whichinaddition,usetheirTCRsforrecognitionofphosphorylatedantigensandstilllargelyundefinedligandsontumorcells.Inthehaploidenticalallo‐HSCTsetting,alloreactiveNKcells,derivedfromdonorHSCs,canexertpotentantileukemiaactivityandkillresidualpatientDCsandTcells,thuspreventingGvHDandgraftrejection.However,generationofKIR+alloreactiveNKcellsfromHSCsrequiresmanyweeks,duringwhichleukemiarelapses,andlife‐threateninginfectionsmayoccur.Importantly,matureNKcellsandγδTcellscancontrolcertaininfectiousagentsefficiently,inparticular,limitCMVreactivation,andinfusionofsuchdonorcellsatthetimeofHSCThasbeenimplemented.Developmentofnovel,cell‐basedimmunotherapies,allowingimprovedtraffickingandbettertargeting,willendowNKcellsandγδTlymphocyteswithenhancedanti‐tumoractivity,alsomakingthemkeyreagentsfortherapiesagainstsolidtumors.TheclinicalaspectsofusingNKcellsandγδTlymphocytesagainsthematologicalmalignancies,includingtheallo‐HSCTcontext,arereviewedintherelatedside‐by‐sidepaperbyLocatelliandcolleagues[1]...

【 授权许可】

CC BY