树突状细胞膜微泡在T细胞激活与结直肠癌细胞杀伤中的作用研究

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【中图分类号】R730.51 【文献标志码】A
Role of dendritic cell membrane microbubbles in the activation of T cells and thekilling of colorectal cancer cells
XuHan',ZhangLiang²,LengXiaojing³,YanShujin',PangHua'
(1.Departmentof NuclearMedicine,TheFirstAfliated Hospitalof Chongqing Medical University;2.Departmentof
Ultrasound,TheFirstAffiliated HospitalofChongqing Medical University;3.Departmentof Ultrasound Medicine, The Second Afliated Hospital of Chongqing Medical University)
【Abstract]Objective:Todesignandevaluateacellmembrane vaccinestrategy basedondendriticcell membrane microbubles (DCM@MBs)ndtexloreitsotentialplicatoninumorimunoterapyseiallyheimunespecific killngofrlls throughtheativationofTcells.Methods:Atfirst,tumorcellembraneproteiswereextractedanddendriccels(DCs)weractivatedtoconfirmthattumorantigenscouldeffectivelystimulatethematurationofimmatureDCs.MatureDC membraneswere then mixedwith lipidstoprepareCM@MBs,whichwereharacterizedformorphology,size,andproteincompositionbycofocallaser scaningmicrosopyandsumdodcylsulfate-polycrylamidegelelectrophoresis.Finallyinitrocoultureexperimentseoducted toassesstheeffectofCM@sontheactivationofTcellsandtheirabilitforspecifickillngoftumorcells.Results:Inthe in vitro DC activation experiment,after stimulation with tumor cell membrane proteins,the 25 μg/mL group had a significant increase in the expression level of MHC class II molecule (25.167%±1.203% )on the surface of immature DCs compared with the control group( P<0.001⟩ ,and DCM@MBs presented with microbubbles encapsulated byred cell membranes,with uniform dispersion and a sizeof 1-5μm .Inthein vitroco-cultureexperiment,theamount of INF-γ secreted byT cellswas 120.574±5.179 ) pg/mL in the DCM @ MBs group,significantly enhancing the activation of CD8+ T cells compared with the control group( P <0.001),and furthermore, theimmune-specific killing rateagainst CT26.WT tumor cellswas (30.737±0.216)% ,which was 3.11 times that against 4T1 mouse breast cancer cells (9.893±0.341)% .Conclusion: The DCM@MBs strategy proposed in this study shows significant potential in tumorimmunotherayndcaneffeivelyctivateTcellsandspifcallykillandeliminatetumorcells,hchprovidesnwideasfortu mor immunotherapy.
【Keywords】dendritic cell;immunotherapy;microbubbles;cell membrane;dendritic cell vaccine
近年来,肿瘤免疫治疗已成为继传统手术、化疗和放疗之后的一种革命性治疗[1-2]。(剩余14564字)