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

  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.