Cisplatin selectively downregulated the frequency and immunoinhibitory function of myeloid-derived suppressor cells in a murine B16 melanoma model

• Published in: Immunologic research Vol. 64; no. 1; pp. 160 - 170
• Main Authors: Huang, Xiang, Cui, Shiyun, Shu, Yongqian
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2016; Springer Nature B.V
• Subjects: Allergology; Animals; Antineoplastic Agents - administration & dosage; Biomedical and Life Sciences; Biomedicine; Cell Growth Processes - drug effects; Cellular biology; Chemotherapy; Cisplatin - administration & dosage; Combined Modality Therapy; Cytokine-Induced Killer Cells - immunology; Cytokine-Induced Killer Cells - transplantation; Cytotoxicity, Immunologic; Female; Immunology; Immunosuppression; Immunotherapy, Adoptive - methods; Interferon-gamma - metabolism; Internal Medicine; Medicine/Public Health; Melanoma; Melanoma, Experimental - immunology; Melanoma, Experimental - therapy; Mice; Myeloid Cells - drug effects; Myeloid Cells - immunology; Original Article; Studies; Tumor Burden; Chemotherapeutic drugs; Immunomodulation; Myeloid-derived suppressor cells; Cisplatin
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-015-8734-1

The objective of this study was to investigate the immunomodulatory effect of cisplatin (DDP) on the frequency, phenotype and function of myeloid-derived suppressor cells (MDSC) in a murine B16 melanoma model. C57BL/6 mice were inoculated with B16 cells to establish the murine melanoma model and randomly received treatment with different doses of DDP. The percentages and phenotype of MDSC after DDP treatment were detected by flow cytometry. The immunoinhibitory function of MDSC was analyzed by assessing the immune responses of cocultured effector cells through CFSE-labeling assay, detection of interferon-γ production and MTT cytotoxic assay, respectively. Tumor growth and mice survival were monitored to evaluate the antitumor effect of combined DDP and adoptive cytokine-induced killer (CIK) cell therapy. DDP treatment selectively decreased the percentages, modulated the surface molecules and attenuated the immunoinhibitory effects of MDSC in murine melanoma model. The combination of DDP treatment and CIK therapy exerted synergistic antitumor effect against B16 melanoma. DDP treatment selectively downregulated the frequency and immunoinhibitory function of MDSC in B16 melanoma model, indicating the potential mechanisms mediating its immunomodulatory effect.