Huang Xiang, Cui Shiyun, Shu Yongqian
Department of Medical Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
Immunol Res. 2016 Feb;64(1):160-70. 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.
本研究的目的是在小鼠B16黑色素瘤模型中,研究顺铂(DDP)对髓源性抑制细胞(MDSC)的频率、表型和功能的免疫调节作用。将C57BL/6小鼠接种B16细胞以建立小鼠黑色素瘤模型,并随机接受不同剂量DDP的治疗。通过流式细胞术检测DDP治疗后MDSC的百分比和表型。分别通过CFSE标记试验、干扰素-γ产生检测和MTT细胞毒性试验评估共培养效应细胞的免疫反应,分析MDSC的免疫抑制功能。监测肿瘤生长和小鼠存活情况,以评估DDP与过继性细胞因子诱导的杀伤(CIK)细胞联合治疗的抗肿瘤效果。在小鼠黑色素瘤模型中,DDP治疗选择性地降低了MDSC的百分比,调节了其表面分子,并减弱了MDSC的免疫抑制作用。DDP治疗与CIK治疗联合对B16黑色素瘤发挥了协同抗肿瘤作用。DDP治疗选择性地下调了B16黑色素瘤模型中MDSC的频率和免疫抑制功能,表明了介导其免疫调节作用的潜在机制。