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干扰肿瘤微环境对细胞毒性T淋巴细胞瘤体内归巢和杀伤活性的影响
引用本文:徐伟立,蔡建辉,李索林,问明,温军业.干扰肿瘤微环境对细胞毒性T淋巴细胞瘤体内归巢和杀伤活性的影响[J].肿瘤防治研究,2014,41(12):1286-1291.
作者姓名:徐伟立  蔡建辉  李索林  问明  温军业
作者单位:050000 石家庄,河北医科大学第二医院小儿外科
摘    要:目的 探讨应用低剂量环磷酰胺(cyclophosphamide, CYC)干扰荷瘤小鼠体内微环境对改善过继回输的细胞毒性T淋巴细胞(cytotoxic T lymphocyte, CTL)瘤体内归巢和杀伤活性的作用。方法 建立C57BL/6荷瘤小鼠模型并分为对照组、CYC注入(CYCI)组、0.9%NaCl溶液注入(NSI)+CTL组和CYCI+CTL组,每组40只,分别给CYCI组、CYCI+CTL组每只小鼠腹腔注入CYC (20mg/kg),NSI+CTL组小鼠注入等量0.9%NaCl溶液。检测注射前后不同时间小鼠瘤体内调节性T细胞(Treg)、白细胞介素-10(IL-10)和转化生长因子-β(TGF-β)水平变化。于注射后第4天回输CFSE-CTL,每只0.2 ml,含5×l06个细胞。流式检测对比NSI+CTL组和CYCI+CTL组瘤体内CFSE-CTL比例。结果 NSI+CTL组小鼠Treg、IL-10、TGF-β水平随着瘤体增长而逐渐增高;CYCI+CTL组比NSI+CTL组回输的CFSE-CTL在肿瘤内归巢明显增加和持久(P<0.05)。各组肿瘤体积除对照组和CYCI组外,其余各组间差异均有统计学意义(P<0.05)。结论 提前应用低剂量CYC干预荷瘤小鼠体内微环境,可降低瘤体内Treg、IL-10和TGF-β水平,使过继回输的CTL在肿瘤中的归巢聚集明显增强,杀伤肿瘤效率提高。

关 键 词:过继性免疫治疗  细胞毒性T淋巴细胞  肿瘤微环境  免疫逃逸  
收稿时间:2013-11-15

Effect of Interfering Tumor Microenvironment on Homing and Killing Activity of Cytotoxic T Lymphocytes
XU Weili,CAI Jianhui,LI Suolin,WEN Ming,WEN Junye.Effect of Interfering Tumor Microenvironment on Homing and Killing Activity of Cytotoxic T Lymphocytes[J].Cancer Research on Prevention and Treatment,2014,41(12):1286-1291.
Authors:XU Weili  CAI Jianhui  LI Suolin  WEN Ming  WEN Junye
Institution:Department of Pediatric Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
Abstract:Objective To explore the effect of interfering tumor microenvironment with low-dosecyclophosphamide (CYC) administration on homing and killing activity of adoptive transfused cytotoxicT lymphocytes in adoptive immunotherapy. Methods Melanoma-bearing mice models were establishedand randomly divided into four groups: control group, CYC injection group (CYCI), the solution of 0.9%w/v of NaCl injection plus CTL infusion group (NSI+CTL) and CYC injection plus CTL infusion group(CYCI+CTL), 40 cases in each group. CYC (20 mg/kg) were intraperitoneally injected in mice of CYCIgroup and CYCI+CTL group. The same amount of the solution of 0.9% w/v of NaCl was injected in mice ofNSI+CTL group. The levels of Treg, TGF-β and IL-10 were detected at the different time points before andafter CYC or the solution of 0.9% w/v of NaCl injection. The cultured CFSE-CTLs were transfused at the4th day after injection, 5×l06 cells per mouse. Then, CFSE-CTLs ratio was analyzed by FCM. Results InNSI+CTL group, the levels of Treg, TGF-β and IL-10 were all increased continuously with tumor growth.CFSE-CTLs ratio in CYCI+CTL group was significantly higher and lasted longer than that in NSI+CTLgroup (P<0.05). There was significant difference among every two group, except control group and CYCIgroup(P<0.05). Conclusion Tumor microenvironment in tumor-bearing mice could be effectivelyintervened by low-dose CYC administration in advance, with decreased Tregs, IL-10, and TGF-β levels. As aresult, more transferred CTLs homing leads to the strenthened killing efficacy.
Keywords:Adoptive cellular immunotherapy  Cytotoxic T lymphocytes  Tumor microenvironment  Immune  escape  
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