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目的通过观察不同剂量的顺铂(Cisplatin,DDP)对B16黑色素瘤荷瘤鼠髓源性抑制细胞(myeloid-derived suppressor cells,MDSCs)的下调作用,探讨介导DDP免疫调节作用的机制。方法建立C57BL/6鼠B16黑色素瘤模型,随机分为三组:生理盐水(normal saline,NS)组:予NS;DDP 2.5 mg/kg组:予DDP 2.5 mg/kg,ip;DDP 5 mg/kg组:予DDP 5 mg/kg,ip。流式细胞术检测DDP处理后荷瘤鼠肿瘤组织、外周血中MDSCs、CD3+T细胞及自然杀伤(natural killer,NK)细胞比例的变化。绘制肿瘤生长曲线比较不同剂量的DDP对细胞因子诱导的杀伤细胞(cytokine-induced killer cells,CIK cells)抑瘤作用的增效作用。结果 DDP可显著降低肿瘤组织中MDSCs的比例(P<0.05),而对外周血中CD3+T细胞及NK细胞的比例无显著作用;两种剂量的DDP(2.5 mg/kg vs.5 mg/kg)对MDSCs的下调作用无显著差异。DDP预处理可显著增强CIK细胞对B16黑色素瘤的抑制作用(P<0.05);此种增效作用在DDP的两种剂量组(2.5 mg/kg vs.5 mg/kg)间无统计学差异。结论在B16黑色素瘤模型中,DDP预处理可增强CIK细胞免疫治疗的疗效,且此种增效作用与DDP选择性下调肿瘤组织中MDSCs的比例相关。
Objective To observe the down-regulation effect of different doses of Cisplatin (DDP) on myeloid-derived suppressor cells (MDSCs) in B16 melanoma and to explore the mechanism of DDP-mediated immunoregulation. Methods C57BL / 6 murine B16 melanoma model was established and randomly divided into three groups: normal saline (NS) group: NS; DDP 2.5 mg / kg group: DDP 2.5 mg / kg group: given DDP 5 mg / kg, ip. The percentage of MDSCs, CD3 + T cells and natural killer (NK) cells in the tumor tissue of the tumor-bearing mice after DDP treatment were detected by flow cytometry. Tumor growth curves were plotted to compare the synergistic effects of different doses of DDP on the cytotoxicity of cytokine-induced killer cells (CIK cells). Results DDP could significantly reduce the proportion of MDSCs in tumor tissue (P <0.05), but had no effect on the proportion of CD3 + T cells and NK cells in peripheral blood. DDP (2.5 mg / kg vs 5 mg / kg) had no significant difference on the down-regulation of MDSCs. DDP pretreatment significantly enhanced the inhibitory effect of CIK cells on B16 melanoma (P <0.05). This synergistic effect was not statistically different between the two doses of DDP (2.5 mg / kg vs 5 mg / kg) . Conclusion In the B16 melanoma model, pretreatment with DDP can enhance the efficacy of CIK cell immunotherapy, and this synergistic effect is related to the selective reduction of the proportion of MDSCs in the tumor tissue by DDP.