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

Cisplatin selectively downregulated the frequency and immunoinhibitory function of myeloid-derived suppressor cells in a murine B16 melanoma model
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顺铂选择性下调小鼠 B16 黑色素瘤模型中骨髓源性抑制细胞的频率和免疫抑制功能

DOI:
10.1007/s12026-015-8734-1
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发表时间:
2016-02-01
影响因子:
4.4
通讯作者:
Shu, Yongqian
Shu, Yongqian
中科院分区:
医学4区
文献类型:
--
作者:
Huang, Xiang;Cui, Shiyun;Shu, Yongqian

文献摘要

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本研究旨在探讨顺铂(DDP)对小鼠B16黑色素瘤模型中髓系抑制细胞(MDSC)频率、表型和功能的影响。C57BL/6小鼠接种B16细胞建立小鼠黑色素瘤模型,随机给予不同剂量的顺铂治疗。流式细胞仪检测DDP处理后MDSC的百分率和表型。通过CFSE标记法、干扰素-γ生成量检测和MTT法检测共培养效应细胞的免疫应答,分析其免疫抑制作用。观察肿瘤生长和小鼠存活情况,评价顺铂和过继细胞因子诱导杀伤(CIK)细胞联合治疗的抗肿瘤作用。DDP可选择性地降低MDSC在黑色素瘤模型中的百分率,调节其表面分子,减弱MDSC的免疫抑制作用。顺铂联合CIK治疗对B16黑色素瘤具有协同抗肿瘤作用。顺铂选择性下调B16黑色素瘤模型中MDSC的频率和免疫抑制功能,提示其免疫调节作用的可能机制。
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.