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1、CHAPTER31TUMORIMMUNOLOGYANDIMMUNOTHERAPYJamesS.Economou,JamesC.Yang,andJamesS.Tomlinsonandproliferatingwithinthethymussurvivethiseducationoverviewoftumorimmunology+process.SeveraltypesofTcellsemergeintotheperiphery.CD8strategiesforclinicaltumorimmunotherapyTcellsrecognizeantigeninth
2、econtextofMHCclassImole-conclusioncules,expressαβTCR,havecytotoxicactivity,andproduce+cytokines.CD4Tcellsrecognizeantigeninthecontextof+MHCclassIImolecules.ThereareseveralsubsetsofCD4TTheimmunesystemisourmostpowerfuldefenseagainstinfec-cells(Fig.31-1).AmongthebetterrecognizedareTh1c
3、ells1tiousdiseaseandthemediatorofrejectionintransplantation.(helpertype1Tcells)thatsecreteinterleukin-2(IL-2),tumorInasmallsubsetofpatients,modernimmune-basedtherapiesnecrosisfactorα(TNF-α),andinterferon-γ(IFN-γ)andTh2canalsoeffectdramaticanddurablerejectionofbulkymetastaticcells,wh
4、ichproduceIL-4,IL-5,IL-6,IL-10,andIL-13.Th1melanomaandrenalcellcancer.ThisatteststothecapacityofcellspromotecytotoxicityandinflammationwhereasTh2cellstheadaptive,andperhapsinnate,immunesystemtorecognizeassistinthestimulationofBcellstoproduceantibody.Thelperanddestroymalignancies.The
5、secompleteresponses,howevercellswillfavoraTh1(cell-mediated)orTh2(humoral)immunefew,aredurable,andpatientsrarelyrelapse,whichisevenmoreresponse,butasubsetofregulatorycells(Tregcells)playsaremarkable.Perhapsthemostimportantobservation,whichhascriticalroleindampeningautoimmunity.These
6、Tregconstitute+beenconfirmedrepeatedlyoverthelast2decades,isthatthe5%to10%ofCD4cellsandexpressthetranscriptionfactorhumanimmunesystemrecognizesself-antigensexpressedinFoxp3.MutationoftheFoxp3geneinhumansandmiceleadsthecontextofmajorhistocompatibilitycomplex(MHCs)ontomultiorganautoim
7、munedisease.AfourthtypeofTcellthecellsurface.AlmosthalfofthehumanTcellrepertoiresubtypeistheso-calledTh17cell,whichpreferentiallyproducesrecognizesself—thesegenerallylow-affinityself-reactiveTcellsIL-17,IL-21,andIL-22andisimportantinthepathogenesishavingescapedthymicdeletion—whichun
8、derscoresthereality
