Dopamine inhibits the function of Gr‐1+CD115+ myeloid‐derived suppressor cells through D1‐like receptors and enhances anti‐tumor immunity

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Dopamine inhibits the function of Gr‐1+CD115+ myeloid‐derived suppressor cells through D1‐like receptors and enhances anti‐tumor immunity

机译：多巴胺通过类D1受体抑制Gr-1 + CD115 +髓样抑制细胞的功能并增强抗肿瘤免疫力

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MDSCsaccumulateintumor‐bearinganimalsandcancerpatientsandareamajorfactorresponsibleforcancer‐inducedimmunosuppressionthatlimitseffectivecancerimmunotherapy.StrategiesaimedateffectivelyinhibitingthefunctionofMDSCsareexpectedtoenhancehostanti‐tumorimmunityandimprovecancerimmunotherapysignificantly.TheneurotransmitterDAhasbeenfoundtohaveanti‐canceractivity,buttheunderlyingmechanismispoorlyunderstood.Inthisstudy,wesoughttoinvestigatethetherapeuticmechanismandefficacyofDAontheinhibitionofcancerdevelopmentviatheregulationofMDSCfunctions.TheregulationofthesuppressivefunctionofGr‐1+CD115+MDSCsbyDAwasdeterminedbyuseofmurinesyngeneicLLCandB16graftmodelstreatedwithDAinvivo,aswellasGr‐1+CD115+MDSCsisolatedfromthesemodeltreatedwithDAexvivo.Here,weshowthatGr‐1+CD115+monocyticMDSCsexpressD1‐likeDAreceptors.DAdramaticallyattenuatedtheinhibitoryfunctionoftumor‐inducedmonocyticMDSCsonTcellproliferationandIFN‐γproductionviaD1‐likeDAreceptorsandretardedtumorgrowth.DAandotherD1receptoragonistsinhibitedIFN‐γ‐inducedNOproductionbyMDSCsfromtumor‐bearingmiceandcancerpatients.DecreasedNOproductionwas,inpart,mediatedviathesuppressionofp‐ERKandp‐JNK.Inconclusion,theneurotransmitterDApotentlyinhibitsthesuppressivefunctionofMDSCandenhancesanti‐tumorimmunity.OurfindingprovidesamechanisticbasisfortheuseofDAorD1‐likereceptoragoniststoovercometumor‐inducedimmunosuppressionincancerimmunotherapy...

机译：MDSCsaccumulateintumor-bearinganimalsandcancerpatientsandareamajorfactorresponsibleforcancer-inducedimmunosuppressionthatlimitseffectivecancerimmunotherapy.StrategiesaimedateffectivelyinhibitingthefunctionofMDSCsareexpectedtoenhancehostanti-tumorimmunityandimprovecancerimmunotherapysignificantly.TheneurotransmitterDAhasbeenfoundtohaveanti-canceractivity，buttheunderlyingmechanismispoorlyunderstood.Inthisstudy，wesoughttoinvestigatethetherapeuticmechanismandefficacyofDAontheinhibitionofcancerdevelopmentviatheregulationofMDSCfunctions.TheregulationofthesuppressivefunctionofGr-1 + CD115 + MDSCsbyDAwasdeterminedbyuseofmurinesyngeneicLLCandB16graftmodelstreatedwithDAinvivo，aswellasGr-1 + CD115 + MDSCsisolatedfromthesemodeltreatedwithDAexvivo.Here，weshowthatGr-1 + CD115 + monocyticMDSCsexpressD1-likeDAreceptors.DAdramaticallyattenuatedtheinhibitoryfunctionoftumor- D1样DA受体和延迟肿瘤生长诱导单核细胞MDSCson T细胞增殖和IFNγ产生.DA和其他D1受体激动剂抑制IFNγ MDSCs诱导来自荷瘤小鼠和癌症患者的NO产生.NO产生的减少部分是通过抑制p-ERK和p-JNK介导的。结论是，神经递质DA可能抑制MDSC的抑制功能并增强抗肿瘤免疫力，从而可以为我们的研究提供一种类似的方法。

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《Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society》 |2015年第1期|共10页
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1. Dopamine inhibits the function of Gr-1(+)CD115(+) myeloid-derived suppressor cells through D1-like receptors and enhances anti-tumor immunity [J] . Wu Jin, Zhang Ruihua, Tang Ning, Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society . 2015,第1期

机译：多巴胺通过类D1受体抑制Gr-1（+）CD115（+）髓样抑制细胞的功能，并增强抗肿瘤免疫力
2. Gr‐1intCD11b+ myeloid‐derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival [J] . Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society . 2016,第6期

机译：Gr-1intCD11b +骨髓来源的抑制细胞在同种异体角膜中积累并提高了同种异体角膜的存活率
3. Silibinin inhibits accumulation of myeloid‐derived suppressor cells and tumor growth of murine breast cancer [J] . Mohammad R. Khorramizadeh, Parvin Forghani Cancer Medicine . 2014,第2期

机译：水飞蓟宾抑制鼠髓样来源的抑制细胞的积累和肿瘤的生长
4. AT1412: A Patient-Derived Antibody Targeting the Tetraspanin CD9 Inhibits Tumor Progression by Stimulating the Influx of Immune Cells [C] . Koen Wagner, Remko Schotte, Els Verdegaal, Protein Engineering Summit. . 2018

机译：AT1412：靶向Tetraspanin CD9的患者衍生的抗体通过刺激免疫细胞的膨胀来抑制肿瘤进展
5. Cancer-associated immunodeficiency and dendritic cell dysfunction: 1. Mediated by the prostaglandin receptor EP2. 2. Myeloid immune suppressor cells in tumor-host interaction. [D] . Yang, Li. 2004

机译：癌症相关的免疫缺陷和树突状细胞功能障碍：1.由前列腺素受体EP2介导。 2.髓样免疫抑制细胞在肿瘤与宿主之间的相互作用。
6. Dopamine inhibits the function of Gr-1+CD115+ myeloid-derived suppressor cells through D1-like receptors and enhances anti-tumor immunity [O] . Jin Wu, Ruihua Zhang, Ning Tang, -1

机译：多巴胺通过类D1受体抑制Gr-1 + CD115 +髓样抑制细胞的功能并增强抗肿瘤免疫力
7. Dopamine receptor type 2 (dopamine receptor type 2) inhibits non-functioning human pituitary tumor-derived cell line HP75 migration through ROCK-mediated cofilin inactivation [O] . Donatella Treppiedi, Erika Peverelli, Elena Giardino, 2014

机译：多巴胺受体型2（多巴胺受体2型）抑制无功能性人垂体肿瘤衍生的细胞系HP75通过岩石介导的Cofilin灭活

Dopamine inhibits the function of Gr‐1+CD115+ myeloid‐derived suppressor cells through D1‐like receptors and enhances anti‐tumor immunity

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