title: Cisplatin selectively downregulated the frequency and immunoinhibitory function of myeloid-derived suppressor cells in a murine B16 melanoma model.
abstract: 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.
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Cui
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. dmo_njmu@163.com.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D048708:Cell Growth Processes / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000276:immunology* / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D005260:Female; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D007371:Interferon-gamma; D002945:Cisplatin
keywords: Chemotherapeutic drugs; Cisplatin; Immunomodulation; Myeloid-derived suppressor cells