Monocyte‐derived dendritic cells from breast cancer patients are biased to induce CD4+CD25+Foxp3+ regulatory T cells

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

关键词: cancer;    tumor immunology;    tolerance;   

DOI  :  10.1189/jlb.0112048

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

DCsorchestrateimmuneresponsescontributingtothepatternofresponsedeveloped.Incancer,DCsmayplayadysfunctionalroleintheinductionofCD4+CD25+Foxp3+Tregs,contributingtoimmuneevasion.WeshowherethatMo‐DCsfrombreastcancerpatientsshowanalteredphenotypeandinducepreferentiallyTregs,aphenomenonthatoccurredregardlessofDCmaturationstimulus(sCD40L,cytokinecocktail,TNF‐α,andLPS).TheMo‐DCsofpatientsinducedlowproliferationofallogeneicCD3+CD25negFoxp3negcells,whichafterbecomingCD25+,suppressedmitogen‐stimulatedTcells.Contrastingly,Mo‐DCsfromhealthydonorsinducedastrongerproliferativeresponse,alowfrequencyofCD4+CD25+Foxp3+withnosuppressiveactivity.Furthermore,healthyMo‐DCsinducedhigherlevelsofIFN‐γ,whereastheMo‐DCsofpatientsinducedhigherlevelsofbioactiveTGF‐β1andIL‐10incocultureswithallogeneicTcells.Interestingly,TGF‐β1blockingwithmAbincocultureswasnotenoughtocompletelyreverttheMo‐DCsofpatientsˈbiastowardTreginduction.Altogether,thesefindingsshouldbeconsideredinimmunotherapeuticapproachesforcancerbasedonMo‐DCs...

【 授权许可】

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