摘要
Humanendogenousretroviruses(HERVs)areretrovirusesthatinfectedhumangenomemillionsofyearsagoandhavepersistedthroughouthumanevolution.About8%ofourgenomeiscomposedofHERVs,mostofwhicharenonfunctionalbecauseofepigeneticcontrolordeactivatingmutations.However,acorrelationbetweenHERVsandhumancancerhasbeendescribedandmanytumors,suchasmelanoma,breastcancer,germcelltumors,renalcancerorovariancancer,expressHERVproteins,mainlyHERV-K(HML6)andHERV-K(HML2).AlthoughthecausativeroleofHERVsincanceriscontroversial,datafromanimalmodelsdemonstratedthatendogenousretrovirusesarepotentiallyoncogenic.HERVproteinexpressioninhumancellsgeneratesanimmuneresponsebyactivatinginnateandadaptiveimmunities.SomeHERV-derivedpeptideshaveantigenicproperties.Forexample,HERV-K(HML-6)encodestheHER-KMELpeptiderecognizedbyCD8+lymphocytes.Inaddition,HERVsaretwoedgedimmunomodulators.HERVsshowimmunosuppressiveactivity.Thepresenceofgenomicretroviralelementsinhost-cellcytosolmayactivateaninterferontypeIresponse.Therefore,targetingHERVsthroughcellularvaccinesorimmunomodulatorydrugscombinedwithcheckpointinhibitorsisattractinginterestbecausetheycouldbeactiveinhumantumors.
出版日期
2016年04月14日(中国Betway体育网页登陆平台首次上网日期,不代表论文的发表时间)