Objective:Elevated myeloid-derived suppressor cells(MDSCs)in many malignancies are associated with the increased risk for metastases and poor prognosis.Therefore,a mouse model of intraocular melanoma was established to explore how MDSCs influence liver metastases.Methods:In this study,murine B16LS melanoma cells were transplanted into the posterior compartment(PC)of the eye of C57BL/6 mice.Leucocytes from the liver of naive mice and mice bearing melanoma liver metastasis were isolated using isotonic Percoll centrifugation,examined by flow cytometry for their expression of Gr1,CD11b,F4/80,RAE-1,and Mult-1,and further isolated for MDSCs and natural killer(NK)cells.The effects of MDSCs on NK cells were tested by co-culturing and assessing the ability of NK cells to produce interferon-gamma(IFN-γ)by ELISA and NK cell cytotoxicity by 3H-thymidine incorporation assay.The impact of IFN-y on liver metastases was examined via selectively depleting IFN-γ in vivo.Results:The results showed that mice with liver metastases had increased levels of CD11b+Gr1+F4/80+as well as CD11b+Gr1+F4/80-MDSCs.MDSCs significantly enhanced the generation of IFN-γ together with the cytotoxicity of the NK cells.Furthermore,these effects were cell-cell contact-dependent.Although IFN-y was not of a toxic nature to the melanoma cells,it profoundly inhibited B16LS cell proliferation.Depleting IFN-γ in vivo led to increased liver metastases.Conclusion:All these findings first revealed that MDSCs accumulated in liver metastasis of intraocular melanoma could activate the NK cells to produce an effective anti-tumor immune response.Thus,the MDSCs'performance in different tumor models would need more investigation to boost current immunotherapy modalities.

Yuan-yuan WANG;Shuang-ying LI;San-qian CHEN;Liang-liang WANG;Zhi-qiang HAN

Department of Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Obstetrics and Gynecology,Chibi People's Hospital,Chibi 437300,China

当代医学科学(英文)

[1]Yuan-yuan WANG;Shuang-ying LI;San-qian CHEN;Liang-liang WANG;Zhi-qiang HAN-.Myeloid-derived Suppressor Cells Activate Liver Natural Killer Cells in a Murine Model in Uveal Melanoma)[J].当代医学科学(英文),2022(05):1071-1078

Uveal,B16LS,Leucocytes,isotonic,Gr1,Mult,CD11b+Gr1+F4,80+as

Myeloid,derived,Suppressor,Cells,Activate,Liver,Natural,Killer,Murine,Model,Melanoma,Objective,Elevated,myeloid,suppressor,cells,MDSCs,many,malignancies,are,associated,increased,risk,metastases,poor,prognosis,Therefore,mouse,intraocular,melanoma,was,established,explore,influence,liver,Methods,In,this,study,murine,were,transplanted,into,posterior,compartment,eye,C57BL,mice,from,naive,bearing,metastasis,isolated,using,Percoll,centrifugation,examined,by,flow,cytometry,their,expression,RAE,further,natural,killer,NK,effects,tested,culturing,assessing,ability,produce,interferon,gamma,IFN,cytotoxicity,3H,thymidine,incorporation,assay,impact,via,selectively,depleting,vivo,Results,results,showed,that,had,levels,well,significantly,enhanced,generation,together,Furthermore,these,contact,dependent,Although,nature,profoundly,inhibited,proliferation,Depleting,Conclusion,All,findings,first,revealed,accumulated,could,activate,effective,anti,tumor,immune,response,Thus,performance,different,models,would,need,investigation,boost,current,immunotherapy,modalities

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