Soluble β‐glucan from Grifola frondosa induces tumor regression in synergy with TLR9 agonist via dendritic cell‐mediated immunity

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

关键词: dectin‐;    1;    CpG ODN;    maitake;    immunotherapy;   

DOI  :  10.1189/jlb.1A0814-415RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Thematurationofdendriticcellsintomore‐immunostimulatorydendriticcellsbystimulationwithdifferentcombinationsofimmunologicagentsisexpectedtoprovideefficient,adoptiveimmunotherapyagainstcancer.Solubleβ‐glucanmaitakeD‐fraction,extractedfromthemaitakemushroomGrifolafrondosa,actsasapotentimmunotherapeuticagent,elicitinginnateandadoptiveimmuneresponses,therebycontributingtoitsantitumoractivity.Here,weevaluatedtheefficacyofmaitakeD‐fraction,incombinationwithaToll‐likereceptoragonist,totreattumorsinamurinemodel.OurresultsshowedthatmaitakeD‐fraction,incombinationwiththeToll‐likereceptor9agonist,cytosine–phosphate–guanineoligodeoxynucleotide,synergisticallyincreasedtheexpressionofdendriticcellmaturationmarkersandinterleukin‐12productionindendriticcells,butitdidnotincreaseinterleukin‐10production,generatingstrongeffectordendriticcellswithanaugmentedcapacityforefficientlypriminganantigen‐specific,Thelper1–typeTcellresponse.MaitakeD‐fractionenhancescytosine–phosphate–guanineoligodeoxynucleotide‐induceddendriticcellmaturationandcytokineresponsesinadectin‐1–dependentpathway.Wefurthershowedthatacombinationtherapyusingcytosine–phosphate–guanineoligodeoxynucleotideandmaitakeD‐fractionwashighlyeffective,eitherasadjuvantsfordendriticcellvaccinationorbydirectadministrationagainstmurinetumor.TherapeuticresponsestodirectadministrationwereassociatedwithincreasedCD11c+dendriticcellsinthetumorsiteandtheinductionofinterferon‐γ–producingCD4+andCD8+Tcells.OurresultsindicatethatmaitakeD‐fractionandcytosine–phosphate–guanineoligodeoxynucleotidesynergisticallyactivateddendriticcells,resultingintumorregressionviaanantitumorThelpercell1–typeresponse.Ourfindingsprovidethebasisforapotentantitumortherapyusinganovelcombinationofimmunologicagentsforfutureclinicalimmunotherapystudiesinpatients...

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