自体DC-CIK联合CTL治疗晚期非小细胞肺癌临床效果观察

Clinical observation on efficacy of autologous DC-CIK plus CTL immunotherapy in advanced non-small cell lung cancer patients

目的观察树突状细胞、细胞因子诱导的杀伤细胞（dendriti ccell—cytokine induced killer，DC—CIK）联合细胞毒性T淋巴细胞（cytotoxic T lymphocyte，CTL）治疗晚期非小细胞肺癌（non—smallcelllungcancer，NSCLC）的临床效果。方法回顾性分析2011年1月－2014年6月的63例晚期NSCLC患者免疫细胞治疗后的临床资料。根据患者自愿选择的免疫治疗方法，分成：DC—CIK组（24例）、CTL组（20例）和DC—CIK＋CTL组（19例）。患者在免疫治疗期间均配合局部，125I粒子植入和小剂量口服化疗药VP１6。每组经过2个疗程治疗后4周观察外周血淋巴细胞亚群和细胞因子变化。参照RECIST标准和NCI—CTCAE4．0标准评价近期临床疗效和安全性；根据Karnofsky功能状态评分评估患者生活质量（quality of life，QOL）变化。计量资料以“互蜘”表示，比较采用方差分析，两两分析采用t检验，计数资料比较采用矿检验，P〈0．05为差异有统计学意义。结果三组外周血淋巴细胞亚群治疗前与治疗后对比差异均无统计学意义（均P〉0．05）。治疗后DC—CIK＋CTL组外周血IFN-γ和IL—10水平[（24．17±3．25）、（9．46±1．90）ng／L]与较治疗前[（12．92±1．87）、（12．00±2．43）ng／L]较差异均有统计学意义（均P〈0．05），与治疗后DC—CIK组[（11．35±2．02）、（10．00±1．55）ug／L]及CTL组[（12．31±2．00）、（11．08±1．35）ng／L]比较差异均有统计学意义（均P〈0．05oDC—CIK＋CTL组治疗的客观反应率（objective responserate，ORR）为47．4％，显著高于DC—CIK组（16．7％）和CTL组（15．O％），差异均有统计学意义（均P〈0．05oDC—CIK＋CTL组疾病控制率（disease controlrate，DCR）为94．7％，显著高于DC—CIK组（70．8％）和CTL组（50．0％），差异均有统计学意义（均P〈0．05）。DC—CIK＋CTL组QOL改善率为57．9％，显著高于DC—CIK组（20．8％）、CTL组（25．0％），差异均有统计学意义（均P〈0．05）。三组患者治疗后均未出现3-4级不良反应。结论DC—CIK联合CTL治疗晚期NSCLC，能取得比单纯DC—CIK或CTL治疗更大的近期临床获益。

Objectlve To evaluate the efficacy of dendritic cell-cytokine induced killer （DC-CIK） plus cytotoxic T lymphocyte （CTL）cells immunotherapy in patients with advanced non＇small cell lung cancer（NSCLC）.Methods Clinical data of 63 patients with advanced NSCLC after cell immunotherapy were analyzed retrospectively from January 2011 to June 2014.According to pa- tients＇ voluntary treatment,patients were divided into 3 groups：DC-CIK group;CTL group;DC-CIK plus CTL group .All patients were treated with low-dose VP16 chemotherapy combined with 125I seed implantation brachytherapy during immunotherapy.Cytokine and lymphocyte subsets changes in patients＇ peripheral blood before and 1 month after treatments were measured. Short-term clinical efficacy was evaluated according to RECIST criteria and safety according to NCI-CTCAE 4.0 criteria respectively.The changes of patients＇ quality of life（QOL）were evaluated according to Karnofsky score.Measurement data were compared by t test,count data were compared by chi square test,P〈0.05 as statistically siznificant difference.Results Peripheral bloodlymphocytes subset proporitions did not differ significantly between before immunotherapy and day 30 after immunotherapy（all P〉0.05）.There were significant differences in the levels of IFN-γ and IL-10 between DC-CIK plus CTL group before [（12.92 ±1.87）,（12.00 ± 2.43）ng/L] and after thrapy [（24.17 ± 3.25）,（9.46 ± 1.90）ng/L] and DC-CIK immunotherapy group [（11.35 ± 2.02）, （10.00 ± 1.55）ng/L] or CTL group [（12.31 ± 2.00）,（11.08 ± 1.35）ng/L] （all P〈0.05）.The clinical objective response rate （ORR） and disease control rate （DCR） in DC-CIK plus CTL group were 47.4% and 94.7%,as compared with 16.7%,70.8% in DC-CIK group（a// P〈0.05） and 15.0%,50.0% in CTL group （all P〈0.05）.The QOL improved rate in DC-CIK plus CTL group （57.9%） was signifi- cantly higher than that in DC-CIK group （20.8%） and in CTL group （25.0%）（all P〈0.05）.No grade 3-4 adverse event happened in all cases.Conclusion The data suggested that DC-CIK plus CTL cell immunotherapy could obtain more beneficial effects than only DC-CIK or CTL cell immunotherapy.