目的：探讨粒细胞-巨噬细胞集落刺激因子（GM-CSF）基因修饰的肿瘤细胞疫苗（GM-CSF modified tumor cell vaccine，GVAX）治疗前后黑素瘤患者外周血免疫指标的变化及其对预后的影响。方法：收集2007年10月至2012年12月期间于天津医科大学肿瘤医院接受GVAX治疗的56例黑素瘤患者，采用流式细胞技术检测患者治疗前后外周血CD3+T细胞、CD4+T细胞、CD8+T细胞、调节性T细胞（Treg）、自然杀伤细胞（NK）及树突状细胞（DC1和DC2）的比例，分析治疗前后外周血各免疫细胞比例的变化，并探讨其与患者预后的关系。结果： GVAX治疗后患者外周血CD8+T细胞比例较前升高\[（37.56±12.76）% vs（34.71±12.30）%，P=0.006\]，CD4+T细胞比例降低\[（53.44±13.36）% vs （56.27±1315）%，P=0.017\]，CD4+/CD8+比值降低\[1.61（1.37）vs 1.75（0.71），P=0.009\]。治疗后CD3+T、NK、Treg、DC1、DC2与治疗前的差异无统计学意义（P>0.05）。晚期患者GVAX治疗前外周血CD8+T细胞比例大于均值组与小于均值组相比，中位生存时间显著延长（29.16 vs 13.34个月，P=0.012）。结论： GVAX治疗黑素瘤可增强CD8+T细胞为主的抗肿瘤免疫应答，晚期患者外周血CD8+T细胞比例可作为预测GVAX疗效的指标，为判断预后起到一定的提示作用。

Objective: To evaluate changes in and prognostic value of CD8+ T cells in the peripheral blood of melanoma patients treated with GM-CSF modified tumor cell vaccine (GVAX). Methods: Fifty-six patients with melanoma who underwent GVAX treatment in the Cancer Institute of Tianjing Medical University between October, 2007 and December, 2012 were enrolled in the study. Proportions of CD3+ lymphocytes, CD4+ T cells, CD8+ T cells, regulatory T lymphocytes (Treg), natural killer cells(NK) and dendritic cell (DC1,DC2) before and after GVAX vaccination treatment were determined by flow cytometry. The relationship between the proportion of CD8+ T cells and other immune cells with patient survival at different post-treatment time points was analyzed. Results: The proportion of CD8+ T cells in peripheral blood was significantly higher (P=0.006) after GVAX treatment (37.56±12.76%) than that before the treatment (3471±12.30%). GVAX treatment resulted in significant decreases in the proportion of CD4+ T cells (P=0.017) and the ratio of CD4+ /CD8+ (P=0.009) but showed no significant effect on the proportions of NK cells, Treg cells, DC1 and DC2 cells (P>0.05). Advanced melanoma patients with a proportion of CD8+ T cells above the mean value before vaccination had better overall survival (29.16 months) compared with those with a lower proportion of CD8+ T cells (1334 months) (P=0.012). Conclusion: GVAX can enhance the ability of CD8+ T cells to induce antitumor immunity. A high proportion of CD8+ T cells before GVAX vaccination is a predictor of better prognosis for patients with advanced melanoma.

国家重点基础研究发展计划（973计划）资助项目（No．2012CB9333004） ; 天津市科学技术委员会应用基础研究面上项目资助（12JCYBJC16100） 。