Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
HPV16‐associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells | |
关键词: human papillomavirus; cytokines; systemic effects; immune evasion; cell signaling; | |
DOI : 10.1189/jlb.3A0513-282R | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
Tumorsarecomplexstructurescontainingdifferenttypesofcellsandmolecules.Theimportanceofthetumormicroenvironmentintumorprogression,growth,andmaintenanceiswell‐established.However,tumoreffectsarenotrestrictedtothetumormicroenvironment.Moleculessecretedby,aswellascellsthatmigratefromtumors,maycirculateandreachothertissues.Thismaycauseaseriesofsystemiceffects,includingmodulationofimmuneresponses,andinsomecases,leukocytosisandmetastasispromotion.Leukocytosishasbeendescribedasapoorprognosticfactorinpatientswithcervicalcancer.ThemainetiologicalfactorforcervicalcancerdevelopmentispersistentinfectionwithhighoncogenicriskHPV.Ourlaboratoryhasbeenexploringtheeffectsofhighoncogenicrisk,HPV‐associatedtumorsonlymphoidorgansofthehost.Inthepresentstudy,weobservedanincreaseinmyeloidcellproliferationandalterationincellsignalinginAPCsinthespleenoftumor‐bearingmice.Inparallel,wecharacterizedthecytokinessecretedintheinflammatoryandtumorcellcompartmentsinthetumormicroenvironmentandinthespleenoftumor‐bearingmice.WeshowevidenceofconstitutiveactivationoftheIL‐6/STAT3signalingpathwayinthetumor,includingTAMs,andinAPCsinthespleen.WealsoobservedthatIL‐10isacentralmoleculeinthetolerancetowardtumorantigensthroughcontrolofNF‐κBactivation,costimulatorymoleculeexpression,andTcellproliferation.Thesesystemiceffectsovermyeloidcellsarerobustandlikelyanimportantproblemtobeaddressedwhenconsideringstrategiestoimproveanti‐tumorTcellresponses...
【 授权许可】
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