丹参-人参配伍调控MDSCs重塑黑色素瘤免疫微环境的研究

Combination of Danshen and Renshen Regulates MDSCs to Remodel the Immune Microenvironment of Melanoma

  • 摘要:
      目的  研究丹参-人参配伍对鼠源黑色素瘤细胞株B16F10体内外免疫微环境的影响及其干预B16F10血行转移的作用机制。
      方法  体外构建T淋巴细胞-B16F10共培养体系, 流式细胞术检测丹参-人参配伍体外能否增强T淋巴细胞对B16F10的杀伤能力; 构建B16F10小鼠尾静脉血行转移模型, 利用动物活体成像技术、HE染色法观察丹参-人参体内对B16F10肺转移的作用。利用流式细胞术、免疫组化及免疫荧光技术检测荷瘤小鼠体内CD4+、CD8+T细胞、骨髓源性抑制细胞(MDSCs)等免疫细胞数量, 利用qPCR技术检测MDSCs增殖的相关mRNA表达水平。
      结果  丹参-人参配伍体外可增强T淋巴细胞对肿瘤细胞的杀伤能力, 在体可有效抑制小鼠B16F10肺转移, 增强CD4+、CD8+T细胞浸润, 通过抑制MDSCs增殖的相关mRNA表达水平, 进而抑制转移灶MDSCs的表达。
      结论  丹参-人参配伍可通过调控MDSCs重塑黑色素瘤免疫微环境, 达到抑制肿瘤转移的目的。研究为丹参-人参配伍的临床抗肿瘤转移应用奠定基础。

     

    Abstract:
      OBJECTIVE  To observe the effect of the combination of Danshen and Renshen on the immune microenvironment of mouse melanoma cell line B16F10 in vivo and in vitro and its mechanism of inhibiting B16F10 blood metastasis.
      METHODS  T-lymphocyte-B16F10 co-culture system was constructed in vitro. Flow cytometry was used to detect whether the combination of Danshen and Renshen could enhance the killing ability of T-lymphocytes against B16F10 in vitro. The model of B16F10 mouse tail vein blood metastasis was established. The inhibitory effect of the combination of Danshen and Renshen on B16F10 lung metastasis was observed by in vivo imaging and HE pathological staining. In addition, flow cytometry, immunohistochemistry and immunofluorescence techniques were used to detect the number of CD4+, CD8+T cells and MDSCs in tumor-bearing mice, and qPCR was used to detect the mRNA expression level related to the proliferation of MDSCs.
      RESULTS  The combination of Danshen and Renshen could enhance the killing ability of T lymphocytes against tumor cells in vitro, and effectively inhibit B16F10 lung metastasis in mice, and enhance CD4+and CD8+T cell infiltration, which in turn suppressed the number of MDSCs in metastases by inhibiting the mRNA expression of MDSCs proliferation-related cytokines.
      CONCLUSION  The combination of Danshen and Renshen can inhibit tumor metastasis by regulating MDSCs to reshape the immune microenvironment of melanoma. This study lays a foundation for the clinical application of the combination of Danshen and Renshen against tumor metastasis.

     

/

返回文章
返回