GM-CSF修饰肿瘤细胞疫苗治疗前后肺癌患者Treg的变化及其临床意义  

Changes in regulatory T cells of lung cancer patients before and after GM-CSF modified tumor cell vaccine treatment and their clinical significance

作　　者：杜春娟[1,2] 于津浦[2] 李慧[2] 张乃宁[1] 滕艳华[1] 李蓁[1] 安阳[2] 曹水[1,2] 任秀宝[1,2] 

机构地区：[1]天津医科大学附属肿瘤医院生物治疗科,天津300060 [2]天津市肿瘤防治重点实验室,天津300060

出　　处：《中国肿瘤生物治疗杂志》2011年第5期473-479,共7页Chinese Journal of Cancer Biotherapy

基　　金：国家科技攻关计划引导项目资助(No.2005BA740C);天津市科技创新专项资金资助(No.06FZZDSF01500)~~

摘　　要：目的:观察GM-CSF基因修饰的肿瘤细胞疫苗(GM-CSF modified tumor cell vaccine,GVAX)治疗前后肺癌患者外周血中CD4+CD25+调节性T细胞(regulatory T cell,Treg)比例的变化,探讨其与肺癌临床病理特征的关系及对患者生存的影响。方法:选择2007年3月至2010年7月天津医科大学附属肿瘤医院接受GVAX治疗的85例肺癌患者,其中鳞癌28例、腺癌47例、小细胞癌10例,早期(Ⅰ～ⅢA期)23例、晚期(ⅢB～Ⅳ期)62例。流式细胞术检测患者GVAX治疗前后外周血Treg的比例,分析治疗前后Treg比例变化与肺癌临床病理特征和患者生存期的关系。结果:接受GVAX治疗的85例肺癌患者1、3年的生存率分别为69.3%、48.2%,治疗后外周血Treg比例明显下降[(4.86±2.52)%vs(5.52±2.68)%,P<0.05]。患者血清LDH水平正常组治疗后Treg比例明显下降[(4.50±2.23)%vs(5.59±2.76)%,P<0.05],而LDH增高组治疗后Treg比例上升[(6.04±3.07)%vs(5.31±2.48)%,P<0.05];GVAX治疗超过1个疗程者较治疗1个疗程者治疗后Treg比例下降更明显[(-0.39±2.39)%vs(-2.11±1.62)%,P<0.05]。治疗前后外周血Treg比例的变化与患者预后相关,治疗后Treg比例下降组患者中位总生存期(overall survival,OS)明显长于升高组(21个月vs 10个月,P<0.05),晚期肺癌患者中Treg比例下降者的OS延长更明显(18个月vs 8个月,P<0.05)。结论:肺癌患者GVAX治疗前后外周血Treg比例变化可能成为评价GVAX疗效及判断患者预后的免疫指标,GVAX治疗后患者Treg比例的下降提示其疗效和预后都较好。Objective：To observe the alteration in proportion of CD4＋CD25＋ regulatory T cells（Tregs） in the peripheral blood of lung cancer patients treated with GM-CSF modified tumor cell vaccine（GVAX） and its relationship to clinical characteristics and survival rate of lung cancer patients.Methods： Eighty-five lung cancer patients treated with GVAX in Affiliated Tumor Hospital of Tianjin Medical University were enrolled in the present study,including 28 squamous carcinoma,47 adenocarcinoma,10 small cell lung cancers,among which 23 in early stage（Ⅰ~ⅢA）,62 in advanced stage（ⅢB~Ⅳ）.The proportion of Tregs in the peripheral blood before and after GVAX treatment was detected by flow cytometry,and the correlation between the alteration of Treg proportional and clinicopathological characteristics and overall survival of lung cancer patients were analyzed.Results： One-year,3-year survival rates of 85 patients with lung cancer treated with GVAX were 69.3% and 48.2%,respectively.The proportion of Treg in peripheral blood significantly decreased after GVAX treatment（[4.86±2.52]% vs [5.52±2.68]%,P0.05）.The proportion of Tregs significantly decreased in the patients with normal LDH level（[4.50±2.23]% vs [5.59±2.76]%,P0.05） while increased in those with high LDH level（[6.00±3.06]% vs [5.30±2.47]%,P0.05） after GVAX treatment.The proportion of Tregs decreased more dramatically in the patients treated with GVAX more than 1 course than in those patients with only 1 course（[-2.11±1.620]% vs [-0.39±2.39]%,P0.05）.The alteration of Treg proportion after GVAX treatment was tightly related to the prognosis of the patients.Patients with a decrease of Tregs showed longer overall survival（OS） than those displaying an increase of Treg after GVAX treatment（21 months vs 10 months,P0.05）,especially patients in advanced stage（18 months vs 8 months,P0.05）.Conclusion： The alteration of Treg proportion in peripheral blood could be a potential immunological indicator to evaluate the effi

关 键 词：肺癌 GM-CSF修饰肿瘤细胞疫苗 调节性T细胞 乳酸脱氢酶 疗效 预后 疗效评价指标 

分 类 号：R730.54[医药卫生—肿瘤]