Activation of Anti-Tumor Immune Response and Reduction of Regulatory T Cells with Mycobacterium indicus pranii (MIP) Therapy in Tumor Bearing Mice 英文参考文献.docVIP

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Activation of Anti-Tumor Immune Response and Reduction of Regulatory T Cells with Mycobacterium indicus pranii (MIP) Therapy in Tumor Bearing Mice 英文参考文献.doc

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Activation of Anti-Tumor Immune Response and Reduction of Regulatory T Cells with Mycobacterium indicus pranii (MIP) Therapy in Tumor Bearing Mice 英文参考文献

ActivationofAnti-TumorImmuneResponseand ReductionofRegulatoryTCellswithMycobacterium indicuspranii(MIP)TherapyinTumorBearingMice FaizAhmad.,JijuMani.¤a,PawanKumar.,SeenuHaridas¤b,PramodUpadhyay,SangeetaBhaskar* ProductDevelopmentCell-I,NationalInstituteofImmunology,NewDelhi,India Abstract Background: Role of immune system in protecting the host from cancer is well established. Growing cancer however subvertsimmuneresponsetowardsTh2typeandescapefromantitumormechanismofthehost.Activationofbothinnate andTh1typeresponseiscrucialforhostantitumoractivity.Inourpreviousstudyitwasfound,thatMycobacteriumindicus pranii(MIP)alsoknownasM.winducesTh1typeresponseandactivatesmacrophagesinanimalmodeloftuberculosis. Hence,westudiedtheimmunotherapeuticpotentialofMIPinmousetumormodelandtheunderlyingmechanismsforits antitumoractivity. Methodology and Principal Findings: Tumors wereimplanted by injecting B16F10 melanomacells subcutaneously into C57BL/6mice.Usingtheoptimizeddoseandtreatmentregimes,anti-tumorefficacyofheatkilledMIPwasevaluated.InMIP treated group, tumor appeared in only 50–60% of mice, tumor growth was delayed and tumor volume was less as comparedtocontrol.MIPmediatedimmuneactivationwasanalysedinthetumormicroenvironment,tumordraininglymph nodeandspleen.InductionofTh1responseandhigherinfiltrationofimmunecellsinthetumormicroenvironmentwas observedinMIPtreatedmice.Alargefractionoftheseimmunecellswereinactivatedstateasconfirmedbyphenotypicand functionalanalysis.Interestingly,percentageofTregcellsinthetumormilieuoftreatedmicewasless.Wealsoevaluated efficacyofMIPalongwithchemotherapyandfoundabetterresponseascomparedtochemotherapyalone. Conclusion:MIPtherapyiseffectiveinprotectingmicefromtumor.Itactivatestheimmunecells,increasestheirinfiltration intumor,andabrogatestumormediatedimmunesuppression. Citation:AhmadF,ManiJ,KumarP,HaridasS,UpadhyayP,etal.(2011)ActivationofAnti-TumorImmuneResponseandReductionofRegulatoryTCellswith Mycobacteriumindicuspranii(MIP)TherapyinTumorBearingMi