Effect of Cisplatin on the Frequency and Immuno-inhibitory Function of Myeloid-derived Suppressor Cells in A375 Melanoma Model

Asian Pac J Cancer Prev. 2015;16(10):4329-33. doi: 10.7314/apjcp.2015.16.10.4329.

Abstract

Background: To investigate the change of frequency and immuno-inhibitory function of myeloid-derived suppressor cells (MDSCs) after treatment of cisplatin (DDP) in A375 human melanoma model.

Materials and methods: BALB/c nude mice were inoculated with A375 cells to establish the human melanoma model and randomly divided into control group given normal saline (NS) and experimental group treated with DDP (5 mg/ kg). The percentages of MDSCs in the tumor tissue and peripheral blood after DDP treatment were detected by flow cytometry. The proliferation and interferon-γ (IFN-γ) secretion of T cells co-cultured with MDSCs were analyzed through carboxyfluorescein succinimidyl ester (CFSE) labeling assay and enzyme-linked immunospot (ELISPOT) assay, respectively.

Results: In A375 human melanoma model, DDP treatment could significantly decrease the percentage of MDSCs in the tumor tissue, but exerted no effect on the level of MDSCs in peripheral blood. Moreover, DDP treatment could attenuate the immuno-inhibitory function of MDSCs. T cells co-cultured with DDP-treated MDSCs could dramatically elevate the proliferation and production of INF-γ.

Conclusions: DDP can decrease the frequency and attenuate immuno-inhibitory function of MDSCs in A375 melanoma model, suggesting a potential strategy to augment the efficacy of combined immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • CD11b Antigen / analysis
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Proliferation
  • Cisplatin / therapeutic use*
  • Coculture Techniques
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Humans
  • Immune Tolerance / drug effects
  • Interferon-gamma / metabolism
  • Melanoma, Experimental / blood
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Cells / chemistry
  • Myeloid Cells / drug effects
  • Myeloid Cells / immunology*
  • Receptors, Cell Surface / analysis

Substances

  • Antineoplastic Agents
  • CD11b Antigen
  • Receptors, Cell Surface
  • granulocyte receptor 1, mouse
  • Interferon-gamma
  • Cisplatin