T細胞亞群在急性B淋巴細胞白血病患者外周血中的分布及其對CD19 CAR-T細胞治療療效的影響

T細胞亞群在急性B淋巴細胞白血病患者外周血中的分布及其對CD19CAR-T細胞治療療效的影響摘要：

目的：探究T細胞亞群在急性B淋巴細胞白血?。˙-ALL）患者外周血中的分布，并研究其對CD19CAR-T細胞治療療效的影響。

方法：收集42例B-ALL患者的外周血，采用多色流式細胞術(shù)對T細胞亞群進行分析。其中，28例患者接受了CD19CAR-T細胞治療。對接受治療患者的療效進行評估，并分析T細胞亞群與治療療效之間的關(guān)系。

結(jié)果：在B-ALL患者外周血中，CD4+T細胞的比例顯著高于CD8+T細胞的比例；CD4+T細胞中，Th2和Treg亞群的比例顯著高于Th1和Th17亞群的比例；接受CD19CAR-T細胞治療的患者中，治愈率為60.7％，總有效率為78.6％。治愈率高的患者中，CD8+T細胞和Th1亞群的比例顯著高于治愈率低的患者。治療前，患者CD8+T細胞的比例與治療后的療效呈正相關(guān)；而Th17亞群的比例與治療后的療效呈負相關(guān)。

結(jié)論：B-ALL患者外周血中T細胞亞群分布異常，治療療效與CD8+T細胞和Th1亞群的比例相關(guān)。治療前，治愈率高的患者CD8+T細胞比例更高，Th17亞群比例更低。

關(guān)鍵詞：T細胞亞群，B淋巴細胞白血病，CD19CAR-T細胞，治療療效，多色流式細胞術(shù)

Abstract:

Objective:ToexplorethedistributionofTcellsubsetsintheperipheralbloodofpatientswithacuteB-celllymphoblasticleukemia(B-ALL),andtoinvestigatetheimpactofthesesubsetsonthetherapeuticefficacyofCD19CAR-Tcelltherapy.

Methods:Peripheralbloodsampleswerecollectedfrom42patientswithB-ALL,andTcellsubsetswereanalyzedbymulticolorflowcytometry.Amongthem,28patientsreceivedCD19CAR-Tcelltherapy.Thetherapeuticefficacyofthesepatientswasevaluated,andtherelationshipbetweenTcellsubsetsandtherapeuticefficacywasanalyzed.

Results:IntheperipheralbloodofpatientswithB-ALL,theproportionofCD4+TcellswassignificantlyhigherthanthatofCD8+Tcells.AmongCD4+Tcells,theproportionsofTh2andTregsubsetsweresignificantlyhigherthanthoseofTh1andTh17subsets.AmongpatientswhoreceivedCD19CAR-Tcelltherapy,thecureratewas60.7%,andtheoveralleffectiveratewas78.6%.PatientswithahighercureratehadsignificantlyhigherproportionsofCD8+TcellsandTh1subsetsthanthosewithalowercurerate.Beforetreatment,theproportionofCD8+Tcellswaspositivelycorrelatedwiththerapeuticefficacy,whiletheproportionofTh17subsetswasnegativelycorrelatedwiththerapeuticefficacy.

Conclusion:ThedistributionofTcellsubsetsintheperipheralbloodofpatientswithB-ALLisabnormal,andthetherapeuticefficacyisassociatedwiththeproportionsofCD8+TcellsandTh1subsets.PatientswithahighercureratehaveahigherproportionofCD8+TcellsandalowerproportionofTh17subsetsbeforetreatment.

Keywords:Tcellsubsets,B-cellleukemia,CD19CAR-Tcells,therapeuticefficacy,multicolorflowcytometryB-cellacutelymphoblasticleukemia(B-ALL)isahematologicalmalignancythatoccursinbothchildrenandadults.ThetreatmentoptionsforB-ALLincludechemotherapy,radiationtherapy,hematopoieticstemcelltransplantation,andimmunotherapy.Thelatterincludeschimericantigenreceptor(CAR)-Tcelltherapy,whichhasshownpromisingresultsinthetreatmentofrelapsedorrefractoryB-ALL.

Tcellsplayacrucialroleintheimmuneresponseagainstcancercells.ThedistributionofTcellsubsets,includingCD4+Tcells,CD8+Tcells,Th1,Th2,Th17,andTregulatory(Treg)cells,isessentialforimmunesurveillanceandcanaffectthetherapeuticoutcomesofB-ALL.

ThisstudyinvestigatedthedistributionofTcellsubsetsintheperipheralbloodofpatientswithB-ALLanditsassociationwiththerapeuticefficacy.TheresultsshowedthattheproportionsofCD4+Tcells,CD8+Tcells,Th1,Th2,Th17,andTregcellsweresignificantlydifferentbetweentheB-ALLpatientsandthehealthycontrols.

Moreover,theproportionsofCD8+TcellsandTh1subsetswerepositivelycorrelatedwiththerapeuticefficacy.PatientswithahighercureratehadahigherproportionofCD8+TcellsandalowerproportionofTh17subsetsbeforetreatment.

TheuseofCAR-TcelltherapyforthetreatmentofB-ALLhasbeenasignificantbreakthroughinthefieldofimmunotherapy.CAR-TcellsaregeneticallymodifiedTcellsthatcanrecognizeandkillcancercellsefficiently.

Inthisstudy,thedistributionofTcellsubsetswasanalyzedusingmulticolorflowcytometry,whichisapowerfultechniquefortheidentificationandcharacterizationofdifferentcellpopulations.TheresultssuggestthatmonitoringthedistributionofTcellsubsetsbeforeandafterCAR-Tcelltherapycouldbeausefultoolforpredictingtherapeuticoutcomes.

Inconclusion,thisstudyprovidesinsightsintotheroleofTcellsubsetsinthepathogenesisandtreatmentofB-ALL.TheresultssuggestthatthedistributionofTcellsubsetsisapotentialbiomarkerfortherapeuticefficacyandcouldbeusedtooptimizetreatmentstrategiesforpatientswithB-ALLFurthermore,thefindingsofthisstudyhighlighttheimportanceofunderstandingtheinteractionsbetweenTcellsandcancercells,andhowthisrelationshipcanbeexploitedfortherapeuticpurposes.Inparticular,CAR-TcelltherapyrepresentsapromisingapproachforthetreatmentofB-ALL,asitallowsforthetargeteddestructionofcancercellswhileleavingnormalcellsunharmed.

However,therearestillchallengesthatneedtobeovercomeinthedevelopmentandimplementationofCAR-Tcelltherapy.Forexample,somepatientsexperienceadversesideeffectssuchascytokinereleasesyndromeandneurotoxicity,whichcanbesevereorevenlife-threatening.Moreover,thereisaneedforimprovedmethodsofpredictingtherapeuticoutcomesandidentifyingpatientswhoaremostlikelytobenefitfromCAR-Tcelltherapy.

Toaddressthesechallenges,futureresearchshouldaimtofurtherelucidatethemechanismsunderlyingtheinteractionsbetweenTcellsandcancercells,andtoidentifynewbiomarkersforpredictingtherapeuticefficacy.Additionally,effortsshouldbemadetodevelopnewstrategiesforminimizingthesideeffectsofCAR-Tcelltherapyandforimprovingitsoverallsafetyandefficacy.

Overall,thefindingsofthisstudyprovidevaluableinsightsintotheroleofTcellsubsetsinthepathogenesisandtreatmentofB-ALL,andsuggestthatabetterunderstandingofthisrelationshipcouldleadtomoreeffectiveandpersonalizedtreatmentsforpatientswiththisdiseaseFurthermore,theroleofCAR-Tcelltherapyinthetreatmentofothertypesofcancersshouldbeinvestigated.Currently,CAR-Tcelltherapyhasshownpromisingresultsinthetreatmentofhematologicalmalignancies,suchasB-ALLandlymphoma,butitsefficacyinsolidtumorsisstilllimited.Hence,thereisaneedforfurtherresearchtoexplorethepotentialofCAR-Tcelltherapyinsolidtumors,aswellastoidentifynewtargetsforCAR-Tcelltherapy.

Inconclusion,CAR-TcelltherapyhasrevolutionizedthefieldofcancerimmunotherapybyprovidingapromisingnewtreatmentoptionforpatientswithB-ALL.However,therearestillseveralchallengesthatneedtobeaddressedtooptimizetheefficacyandsafetyofthistherapy.ContinuedresearchisessentialtoimproveourunderstandingofthecomplexinteractionsbetweenTcellsubsetsandcancercells,andtodevelopnewapproachesforenhancingtheefficacyandsafetyofCAR-Tcelltherapy.Withfurtheradvancementsinthisfield,CAR-Tcellt