醫(yī)學免疫學英文版課件：Tumor Immunology

TumorImmunologyTumorimmunology:Abranchof

immunology

thatstudiesinteractionsbetweenthe

immunesystemand

tumor

cells(alsocalled

cancers)Itisagrowingfieldofresearchthataimstodiscoverinnovativecancerimmunotherapies

totreatandretardprogressionofthedisease.Theimmuneresponse,includingtherecognitionofcancer-specific

antigens,isofparticularinterestinthefieldasknowledgegaineddrivesthedevelopmentofnewvaccines,antibodytherapies,andtumormarker-baseddiagnostictest.

I.Tumorantigensnewlyexpressedantigensoverexpressedantigens1.Generationoftumorantigensnewlysynthesisedproteinduringcarcinogenesis

genemutationcausesstructuralchangeofnormalproteinglycosylationleadstoabnormalcellproteingeneration

concealedantigenexposureabnormalaggregationofmultiplemembraneprotein

moleculesabnormalhighexpressionofembryonicordifferentiation

antigensClassificationoftumorantigensAccordingtospecificityoftumorantigenTumorspecificantigen,TSA(tumorspecifictransplantationantigen,TSTA)

Tumor-associatedantigen,TAATumorspecificantigen(TSA):presentonlyontumorcellsandnotonanyothercellsMutationof

protooncogenes

and

tumorsuppressorsleadsto

abnormalproteinproduction.(calledtumor-specificantigens)

Tumor-associatedantigen(TAA):presentonsometumorcellsandalsosomenormalcellsMutationofsomegenesunrelatedtothetumorformationmayleadtosynthesisofabnormalproteinswhicharecalled

tumor-associatedantigens.

Accordingtotheoccurrenceoftumor

Tumorantigeninducedbyphysiochemicalfactors

radiation,ultravioletrays,chemicals(methylcholanthrene,MCA)characteristic：

highspecificityweakimmunogenicity

obviousindividualspecificity

Tumor-antigeninducedbyviruses

DNA、RNAvirus EBV→nasopharyngealcancer

HPV→cervicalcarcinoma*aflatoxin(AFT,黃曲霉素)→livercancer

characteristic：

onevirusinducesdifferenttypesofcancer,butexpresssameantigenstrongimmunogeneicity

Spontaneoustumorantigen

Noclearincentives,strongspecificityEmbryonicantigens

Alphafetoprotein,AFP(甲胎蛋白)Carcinoembryonicantigen,CEA(癌胚抗原)

II.MechanismoftumorimmunityCellmediatedimmuneresponseCD8+T(CTL,Tc)CD4+TCTLkillstumorcellspecifically*recognitionstage、effectorstageAgspecificityMHC

restrictionApoptosis:perforin/granzyme

apoptosis:Fas/FasL,TNFKillingmechanismsofcytotoxicTlymphocytesCD4+Tcells：①helpCTLactivation②produceCKtoactivateM

andNK

tokilltumorcells③someCD4+Tcellskilltumorcellsdirectly2.Humoralimmuneresponse

CDCADCC

Abopsonization

Absblockreceptorsontumorcellstoinhibittumorgrowth,adhesionandmetastasis3.NonspecificimmuneresponseNKMNKM：

lysosomalenzymeTNF-

ADCCIII.MechanismsoftumorcellsescapefromimmunesurveillanceLossoftumorantigensandantigenicmodulationDecreaseorabsenceofMHCclassImoleculesLackofco-stimulatorymoleculesonthetumorcellsImmuneinhibitorssecretedbytumorcellsAICDofimmunocytesinducedbytumorcellsGrowthpromptlyoftumorcellsExpressionanti-apoptosismolecules(Bcl)bytumorcellsFactorsrelatedtotumorcellsImmunodeficiencySuppressionofimmunefunction2.Factorsrelatedtothehost’simmunesystemIV.Diagnosis,immunotherapyandpreventionfortumor1.Diagnosisfortumor

Tumorantigenslabeledanti-CEAMetastasisofcoloncancertolungActiveimmunotherapySpecific:TumorvaccineNonspecific:BCG2.Immunotherapyfortumor

TumorvaccineABCDGenemodificationPassiveimmunotherapyTargetimmunotherapy:Abcytokine(G-CSF,IL-2,Interferonetal)Adoptiveimmunotherapy:effectorcell3.Preventionfortumor

vaccineHPV----cervicalcarcinomaReview