Cross‐talk among myeloid‐derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors

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

关键词: cancer;    cytokines;    tumor microenvironment;    IL‐;    6;    IL‐;    10;    nitric oxide;   

DOI  :  10.1189/jlb.3A0414-210R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

MDSCandmacrophagesarepresentinmostsolidtumorsandareimportantdriversofimmunesuppressionandinflammation.Itisestablishedthatcross‐talkbetweenMDSCandmacrophagesimpactsanti‐tumorimmunity;however,interactionsbetweentumorcellsandMDSCormacrophagesarelesswellstudied.Toexaminepotentialinteractionsbetweenthesecells,westudiedtheimpactofMDSC,macrophages,andfourmurinetumorcelllinesoneachother,bothinvitroandinvivo.WefocusedonIL‐6,IL‐10,IL‐12,TNF‐α,andNO,asthesemoleculesareproducedbymacrophages,MDSC,andmanytumorcells;arepresentinmostsolidtumors;andregulateinflammation.InvitrostudiesdemonstratedthatMDSC‐producedIL‐10decreasedmacrophageIL‐6andTNF‐αandincreasedNO.IL‐6indirectlyregulatedMDSCIL‐10.TumorcellsincreasedMDSCIL‐6andviceversa.TumorcellsalsoincreasedmacrophageIL‐6andNOanddecreasedmacrophageTNF‐α.Tumorcell‐drivenmacrophageIL‐6wasreducedbyMDSC,andtumorcellsandMDSCenhancedmacrophageNO.InvivoanalysisofsolidtumorsidentifiedIL‐6andIL‐10asthedominantcytokinesanddemonstratedthatthesemoleculeswereproducedpredominantlybystromalcells.TheseresultssuggestthatinflammationwithinsolidtumorsisregulatedbytheratiooftumorcellstoMDSCandmacrophagesandthatinteractionsofthesecellshavethepotentialtoaltersignificantlytheinflammatorymilieuwithinthetumormicroenvironment...

【 授权许可】

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