基于双人源化小鼠模型探索靶向间质MAOA在前列腺癌免疫微环境中的作用
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1.空军军医大学西京医院泌尿外科;2.空军军医大学实验动物中心

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国家自然科学基金(32270566);空军军医大学第一附属医院航空临床医学专项研究项目(HKLCZX03)


Investigating the role of targeting stromal MAOA in the immune microenvironment of prostate cancer based on a humanized mouse model of two individuals
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1.Department of Urology, Xijing Hospital, Air Force Medical University;2.Laboratory Animal Center, Air Force Medical University

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Funded by the National Natural Science Foundation of China (32070532);The First Affiliated Hospital of Air Force Military Medical University Aviation Clinical Medicine Special Research Project (HKLCZX03)

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    摘要:

    【】 目的 通过构建免疫-肿瘤双人源化小鼠模型,探索靶向间质单胺氧化酶 A (monoamine oxidase A,MAOA)在前列腺癌免疫微环境中的作用。方法 利用生物信息学分析MAOAhigh肿瘤相关成纤维细胞(cancer associated fibroblast,CAF)在前列腺癌中与T细胞的关系;利用多重免疫荧光技术分析间质MAOA与CD8+T细胞的关系;构建免疫-肿瘤双人源化小鼠模型,体内验证靶向间质MAOA后CD8+T细胞浸润情况。结果 间质中MAOA的表达与CD8+T细胞浸润成反比;体内抑制间质中MAOA可以提高CD8+T细胞浸润,这可能是通过抑制肿瘤微环境中胶原的累积所实现的。结论 间质中MAOA在前列腺癌免疫抑制微环境中发挥着重要作用,抑制间质中MAOA的表达可以促进免疫细胞的浸润,提示MAOA抑制剂可能作为前列腺癌患者免疫联合治疗的潜在治疗药物。
    【关键词】:前列腺癌;MAOA;肿瘤相关成纤维细胞;肿瘤免疫微环境

    Abstract:

    【】Objective By constructing an immune-tumor dual humanized mouse model, explore the role of targeting monoamine oxidase A (MAOA) in the immune microenvironment of prostate cancer. Methods Utilize bioinformatics analysis to examine the relationship between MAOAhigh cancer-associated fibroblasts (CAFs) and T cells in prostate cancer; employ multiplex immunofluorescence to analyze the relationship between stromal MAOA and CD8+ T cells; construct an immune-tumor dual humanized mouse model to in vivo verify the infiltration of CD8+ T cells after targeting stromal MAOA. Results The expression of MAOA in the stroma is inversely proportional to the infiltration of CD8+ T cells; inhibiting MAOA in the stroma can enhance the infiltration of CD8+ T cells in vivo, which may be achieved by suppressing the accumulation of collagen in the tumor microenvironment. Conclusion Stromal MAOA plays an important role in the immunosuppressive microenvironment of prostate cancer, and inhibiting stromal MAOA can promote the infiltration of immune cells. MAOA inhibitors may serve as potential therapeutic drugs for immune combination therapy in patients with prostate cancer

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  • 收稿日期:2024-10-09
  • 最后修改日期:2024-12-27
  • 录用日期:2025-05-19
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