HPV16‐associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

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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