小剂量重组人白细胞介素-2维持治疗对肿瘤患儿免疫细胞亚群的影响  

Effect of Low-Dose Recombinant Interleukin-2 Therapy on Immunocyte Subsets in Children with Solid Tumor

作　　者：雷嘉颖 黎阳[1] 李春谋 熊稀霖[1] 冯楚础 翁文骏[1] 彭晓敏[1] 周敦华[1] 黄科[1] LEI Jia-Ying;LI Yang;LI Chun-Mou;XIONG Xi-Lin;FENG Chu-Chu;WENG Wen-Jun;PENG Xiao-Min;ZHOU Dun-Hua;HUANG Ke(Department of Oncology,Children′s Medical Center,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,Guangdong Province,China)

机构地区：[1]中山大学孙逸仙纪念医院儿童医学中心肿瘤科,广东广州510120

出　　处：《中国实验血液学杂志》2024年第2期445-449,共5页Journal of Experimental Hematology

摘　　要：目的:探讨小剂量重组人白介素-2(r IL-2)维持治疗对恶性实体肿瘤患儿免疫细胞亚群的影响及相关副反应。方法:选取2012年12月-2017年11月在本科治疗的22例肿瘤患儿,男女各11例,开始IL-2治疗的中位年龄9(3-16)岁,给予小剂量r IL-2免疫治疗前均完成全部手术及放化疗,其中完全缓解17例,部分缓解5例。化疗结束1个月后开始使用rIL-2小剂量维持治疗:4×10^(5)IU/(m^(2)·d),隔日皮下注射,每周3次,共1年。每3个月行免疫细胞亚群检测至治疗终止,同时随访患儿病情转归及治疗相关副反应。结果:22例患儿经r IL-2治疗后外周血T淋巴细胞(CD3^(+))、自然杀伤细胞(CD3-CD56^(+))、辅助性T细胞(CD3^(+)CD4^(+))、杀伤性T细胞(CD3^(+)CD8^(+))的绝对值及辅助T细胞/抑制T细胞比例均显著升高(均P<0.05),而调节性T细胞(CD4^(+)CD25^(+)CD127^(-))治疗前后的绝对值及比例无显著性差异(P>0.05)。在治疗前获得完全缓解的17例患儿中,14例在治疗后继续保持完全缓解,3例复发,其中2例放弃治疗后死亡;治疗前获得部分缓解的5例患儿经治疗后行PET/CT扫描后评估为完全缓解。在小剂量r IL-2免疫治疗初期,出现注射部位皮疹1例,注射后低至中度一过性发热2例,均给予对症处理后消失,未见治疗相关器官功能损害。结论:小剂量r IL-2维持治疗耐受性良好,可显著改善肿瘤患儿外周血部分抗肿瘤免疫细胞亚群的分布,且不会导致调节性T细胞绝对值及比例的升高。Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4×10^(5) IU/(m^(2)·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3^(+)T cells,CD3-CD56^(+)natural killer cells,CD3^(+)CD4^(+)helper T cells(Th)and CD3^(+)CD8^(+)cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P<0.05).While,there were no significant differences in absolute value and proportion of CD4^(+)CD25^(+)CD127^(-)Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

关 键 词：重组人白介素2 儿童 实体瘤 免疫细胞 调节性T细胞 

分 类 号：R730.51[医药卫生—肿瘤]