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


Background: To investigate the change of frequency and immuno-inhibitory function of myeloid-derivedsuppressor 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 andrandomly 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 byflow cytometry. The proliferation and interferon-γ (IFN-γ) secretion of T cells co-cultured with MDSCs wereanalyzed through carboxyfluorescein succinimidyl ester (CFSE) labeling assay and enzyme-linked immunospot(ELISPOT) assay, respectively.
Results: In A375 human melanoma model, DDP treatment could significantlydecrease the percentage of MDSCs in the tumor tissue, but exerted no effect on the level of MDSCs in peripheralblood. Moreover, DDP treatment could attenuate the immuno-inhibitory function of MDSCs. T cells co-culturedwith 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.