GM-CSF基因修饰肿瘤细胞疫苗治疗前后黑素瘤患者CD8^+T细胞的变化及其对预后的影响  

Changes in and prognostic value of peripheral blood CD8^+T cells in melanoma patients before and after GVAX treatment

作　　者：马晓菲[1,2,3] 钱雅琴[1,2,3] 赵华 于津浦 魏枫 安阳 于文文 李慧 任秀宝[1,2,3] 

机构地区：[1]天津医科大学肿瘤医院生物治疗科,天津300060 [2]国家肿瘤临床医学研究中心,天津300060 [3]天津市肿瘤免疫与生物治疗重点实验室,天津300060

出　　处：《中国肿瘤生物治疗杂志》2015年第2期240-245,共6页Chinese Journal of Cancer Biotherapy

基　　金：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)~~

摘　　要：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.

关 键 词：黑素瘤 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 CD8+T细胞 预后 

分 类 号：R739.5[医药卫生—肿瘤] R730.51[医药卫生—临床医学]