Leprosy as a model to understand cancer immunosurveillance and T cell anergy

[摘要] LeprosyisadiseasecausedbyMycobacteriumlepraethatpresentsonaspectrumofbothclinicalmanifestationsandTcellresponse.Ononeendofthisspectrum,tuberculoidleprosyisawell‐controlleddisease,characterizedbyacell‐mediatedimmunityandimmunosurveillance.Ontheoppositeendofthespectrum,lepromatousleprosyischaracterizedbyM.lepraeproliferationandTcellanergy.Similartoprogressivetumorcells,M.lepraeescapesimmunosurveillanceinmoresevereformsofleprosy.ThemechanismsbywhichM.lepraeisabletoevadethehostimmuneresponseinvolvemany,includingthealterationsoflipiddroplets,microRNA,andSchwanncells,andinvolvetheregulationofimmuneregulators,suchasthenegativecheckpointregulatorsCTLA‐4,programmeddeath1,andV‐domainIgsuppressorofTcellactivation—importanttargetsintoday'scancerimmunotherapies.Themeansbywhichtumorcellsbecomeabletoescapeimmunosurveillancethroughnegativecheckpointregulatorsareevidencedbythesuccessesoftreatments,suchasnivolumabandipilimumab.Manyparallelscanbedrawnbetweentheimmuneresponsesseeninleprosyandcancer.Therefore,theunderstandingofhowM.lepraeencouragesimmuneescapeduringproliferativediseasestateshaspotentialtoaddtoourunderstandingofcancerimmunotherapy...

[学科分类] 生理学

[关键词] Immunoediting;T cell plasticity;exhaustion