SimB16 Modeling Induced Immune System Response against B16-Melanoma 英文参考文献.docVIP

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SimB16 Modeling Induced Immune System Response against B16-Melanoma 英文参考文献.doc

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SimB16:ModelingInducedImmuneSystemResponse againstB16-Melanoma FrancescoPappalardo1.,IvanMartinezForero2.,MarzioPennisi1,AsisPalazon2,IgnacioMelero2*, SantoMotta1 1UniversityofCatania,Catania,Italy,2CIMAandCUNUniversityofNavarraPamplona,Pamplona,Spain Abstract Immunological therapy of progressive tumors requires not only activation and expansion of tumor specific cytotoxic T lymphocytes (CTLs), but also an efficient effector phase including migration of CTLs in the tumor tissue followed by conjugationandkillingoftargetcells.Wereporttheapplicationofanagent-basedmodeltorecapitulateboththeeffectof aspecificimmunotherapystrategyagainstB16-melanomainmiceandthetumorprogressioninagenerictissuesection.A comparisonoftheinsilicoresultswiththeinvivoexperimentsshowsexcellentagreement.Wethereforeusethemodelto predict a critical role for CD137 expression on tumor vessel endothelium for successful therapy and other mechanistic aspects. Experimental results are fully compatible with the model predictions. The biologically oriented in silico model derivedinthisworkwillbeusedtopredicttreatmentfailureorsuccessinotherpre-clinicalconditionseventuallyleading newpromisinginvivoexperiments. Citation:PappalardoF,ForeroIM,PennisiM,PalazonA,MeleroI,etal.(2011)SimB16:ModelingInducedImmuneSystemResponseagainstB16-Melanoma.PLoS ONE6(10):e26523.doi:10.1371/journal.pone.0026523 Editor:VladimirBrusic,Dana-FarberCancerInstitute,UnitedStatesofAmerica ReceivedAugust4,2011;AcceptedSeptember28,2011;PublishedOctober19,2011 Copyright:?2011Pappalardoetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:FinancialsupportwasfromMEC/MICINN(SAF2005-03131andSAF2008-03294),Departamento deEducacio′ndeNavarra(BecaOrtizdeLanda′zuri), RedesTema′ticas deInvestigacio′nCooperativaRETIC(RD06/0020/0065),FondodeInvestigacio′nSanitaria(FISPI060932),Europe