A Systems Immunology Approach to the Host-Tumor Interaction Large-Scale Patterns of Natural Autoantibodies Distinguish Healthy and Tumor-Bearing Mice 英文参考文献.docVIP

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A Systems Immunology Approach to the Host-Tumor Interaction Large-Scale Patterns of Natural Autoantibodies Distinguish Healthy and Tumor-Bearing Mice 英文参考文献.doc

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A Systems Immunology Approach to the Host-Tumor Interaction Large-Scale Patterns of Natural Autoantibodies Distinguish Healthy and Tumor-Bearing Mice 英文参考文献

ASystemsImmunologyApproachtotheHost-Tumor Interaction:Large-ScalePatternsofNatural AutoantibodiesDistinguishHealthyandTumor-Bearing Mice YifatMerbl1¤,RoyiItzchak2,TalVider-Shalit2,YoramLouzoun2,FranciscoJ.Quintana3,EzraVadai1 ,Lea Eisenbach1,IrunR.Cohen1* 1DepartmentofImmunology,TheWeizmannInstituteofScience,Rehovot,Israel,2DepartmentofMathematics,GondaBrainResearchCenter,Bar-IlanUniversity,Ramat- Gan,Israel,3CenterforNeurologicDiseases,BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica Abstract Traditionally,immunologyhasconsideredameaningfulantibodyresponsetobemarkedbylargeamountsofhigh-affinity antibodiesreactivewiththespecificincitingantigen;thedetectionofsmallamountsoflow-affinityantibodiesbindingto seemingly unrelated antigens has been considered to be beneath the threshold of immunological meaning. A systems- biologyapproachtoimmunology,however,suggeststhatlarge-scalepatternsintheantibodyrepertoiremightalsoreflect thefunctionalstateoftheimmunesystem.Toinvestigatesuchglobalpatternsofantibodies,wehaveusedanantigen- microarraydevicecombinedwithinformaticanalysis.Hereweaskedwhetherantibody-repertoirepatternsmightreflectthe stateofanimplantedtumor.Westudiedtheserum antibodiesofinbredC57BL/6mice beforeandafterimplantation of syngeneic 3LL tumor cells of either metastatic or non-metastatic clones. We analyzed patterns of IgG and IgM autoantibodiesbindingtoover300self-antigensarrayedonslidesusingsupportvectormachinesandgeneticalgorithm techniques.Wenowreportthatantibodypatterns,butnotsingleantibodies,wereinformative:1)mice,evenbeforetumor implantation,manifestbothindividualandcommonpatternsoflow-titernaturalautoantibodies;2)thepatternsofthese autoantibodies respond to the growth of the tumor cells, and can distinguish between metastatic and non-metastatic tumor clones; and 3) curative tumor resection induces dynamic changes in these low-titer autoantibody patterns. The informative patterns included autoantibodies bind