您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (7): 19-23.doi: 10.6040/j.issn.1671-7554.0.2014.977

• 基础医学 • 上一篇    下一篇

血管内皮抑素协同肿瘤特异性DC-T细胞的抗肿瘤效应

李星宇, 梁婧, 李岩   

  1. 山东大学附属千佛山医院肿瘤化疗科, 山东 济南 250014
  • 收稿日期:2014-12-21 修回日期:2015-04-28 出版日期:2015-07-10 发布日期:2015-07-10
  • 通讯作者: 李岩。E-mail:liyan16766@163.com E-mail:liyan16766@163.com
  • 基金资助:
    山东省自然科学基金(ZR2010HL015)

Antitumor effect of endostatin synergized with tumor special DC-T cellular therapy

LI Xingyu, LIANG Jing, LI Yan   

  1. Department of Chemotherapy, Cancer Center, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2014-12-21 Revised:2015-04-28 Online:2015-07-10 Published:2015-07-10

PDF (PC)

99

摘要： 目的 探讨血管内皮抑素联合肿瘤特异性DC-T细胞对Lewis肺癌小鼠的抗肿瘤效应。方法 建立Lewis肺癌C57BL/6鼠移植瘤模型, 培养小鼠来源肿瘤特异性DC-T细胞, 随机分为A组(PBS对照组)、B组(DC-T组)及C组(DC-T+血管内皮抑素组)。测量小鼠的体质量及肿瘤组织质量和体积, Western blotting检测各组肿瘤组织内血管内皮生长因子(VEGF)和乏氧诱导因子-1α(HIF-1α)蛋白的表达, 流式细胞术检测肿瘤组织细胞悬液内髓源抑制性细胞(MDSC)、肿瘤相关巨噬细胞(TAM, M1/M2)、成熟的树突状细胞(mDC)和CD8+T细胞的比例。结果 与A组比较,B组(P<0.05)、C组(P<0.01)肿瘤生长明显受到抑制;相较于A组, B组VEGF表达下降, 且HIF-1α表达增加(P<0.05), C组VEGF表达明显下降, 且HIF-1α表达明显增加(P<0.01);与A组比较, B组(P<0.05)、C组(P<0.01)的MDSC和M2型TAM比例下降, M1型TAM升高, 肿瘤组织内mDC和CD8+T细胞比例增加。结论 血管内皮抑素联合肿瘤特异性DC-T细胞治疗明显减缓肿瘤生长, 有效逆转了肿瘤微环境的免疫抑制, 从而发挥了协同抗肿瘤效应。

关键词: 细胞免疫治疗, 肿瘤微环境, 血管内皮抑素, 血管新生, 肺肿瘤

Abstract: Objective To investigate the antitumor effect of endostatin combined with tumor special DC-T cellular therapy on lung cancer in Lewis mice. Methods C57BL/6 mice models were established. Tumor antigen special DC-T cells from spleen cells and mice bones were cultured in vitro. The tumor-bearing mice were randomly divided into three groups: A group (PBS control group), B group (DC-T group), and C group (DC-T+endostatin group). The body weight of mice and tumor volume were measured. The VEGF and HIF-1α expressions were determined with Western blotting. The proportions of MDSC, TAM (M1/M2), mDC and CD8+T in suspended tumor cells of tumor tissues were detected with FCM. Results Compared with that in A group, tumor growth in B group (P<0.05) and C group (P<0.01) were inhibited; VEGF expression decreased while HIF-1α expression increased in B group (P<0.05) and C group (P<0.01); the proportions of MDSC and TAM (M2 type) were reduced, while proportions of mDC, TAM (M1 type) and CD8+T cells were elevated in B group (P<0.05) and C group (P<0.01). Conclusion Tumor special DC-T cells combined with endostatin strongly reduce tumor growth, and efficiently reverse the immunosuppression of tumor microenvironment, exhibiting synergistic and much better antitumor effects than monotherapy strategy.

Key words: Cellular therapy, Angiogenesis, Lung neoplasm, Endostatin, Tumor microenvironment

中图分类号: 

  • R73-36+2
[1] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012[J]. CA Cancer J Clin, 2012, 62(1): 10-29.
[2] Sharma P, Wagner K, Wolchok JD, et al. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps[J]. Nat Rev Cancer, 2011, 11(11): 805-812.
[3] Rosenberg SA. Overcoming obstacles to the effective immunotherapy of human cancer[J]. Proc Natl Acad Sci U S A, 2008, 105(35): 12643-12644.
[4] Keibel A, Singh V, Sharma MC. Inflammation, microenvironment, and the immune system in cancer progression[J]. Curr Pharm Des, 2009, 15(17): 1949-1955.
[5] Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer[J]. Cell, 2010, 140(6): 883-899.
[6] Vasievich EA, Huang L. The suppressive tumor microenvironment: a challenge in cancer immunotherapy[J]. Mol Pharm, 2011, 8(3): 635-641.
[7] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5): 646-674.
[8] Sonpavde G, Agarwal N, Choueiri TK, et al. Recent advances in immunotherapy for the treatment of prostate cancer[J]. Expert Opin Biol Ther, 2011, 11(8): 997-1009.
[9] Ko JS, Zea AH, Rini BI, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients[J]. Clin Cancer Res, 2009, 15(6): 2148-2157.
[10] Ozao-Choy J, Ma G, Kao J, et al. The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies[J]. Cancer Res, 2009, 69(6): 2514-2522.
[11] Rosenberg SA. Cell transfer immunotherapy for metastatic solid cancer-what clinicians need to know[J]. Nat Rev Clin Oncol, 2011, 8(10): 577-585.
[12] Griffioen AW. Anti-angiogenesis: making the tumor vulnerable to the immune system[J]. Cancer Immunol Immunother, 2008, 57(10): 1553-1558.
[13] De Bock K, Mazzone M, Carmeliet P. Antiangiogenic therapy, hypoxia, and metastasis: risky liaisons, or not?[J]. Nat Rev Clin Oncol, 2011, 8(7):393-404.
[14] Teicher BA. Antiangiogenic agents and targets: a perspective[J]. Biochem Pharmacol, 2011, 81(1): 6-12.
[15] Schoenfeld J, Jinushi M, Nakazaki Y, et al. Active immunotherapy induces antibody responses that target tumor angiogenesis[J]. Cancer Res, 2010, 70(24): 10150-10160.
[16] Nair S, Boczkowski D, Moeller B, et al. Synergy between tumor immunotherapy and antiangiogenic therapy[J]. Blood, 2003, 102(3): 964 -971.
[17] Ebos JM, Kerbel RS. Antiangiogenic therapy: impact on invasion, disease progression, and metastasis[J]. Nat Rev Clin Oncol, 2011, 8(4): 210-221.
[1] 黄竹青,吴雪韦,任冬梅. 槲寄生中酚类化学成分的分离鉴定及其对A549细胞的增殖抑制活性[J]. 山东大学学报（医学版）, 2017, 55(8): 35-41.
[2] 曾奕明,林燕萍. 放射性125I粒子植入局部治疗支气管肺癌[J]. 山东大学学报（医学版）, 2017, 55(4): 1-6.
[3] 霍彬,王磊,王海涛,霍小东,曹强,王丽丽,臧立,王金焕,郑广钧, 柴树德. 模板联合肋骨钻孔技术辅助放射性粒子植入治疗肺癌的可行性[J]. 山东大学学报（医学版）, 2017, 55(2): 26-31.
[4] 韩明勇,霍彬,张颖,林琦,戴建建,徐瑞彩,杨琦,耿宝成,郑广钧,王海涛,霍小东,陈宝明(柴树德,王俊杰审阅). CT联合模板引导放射性粒子植入治疗肺癌技术流程[J]. 山东大学学报（医学版）, 2017, 55(2): 14-20.
[5] 路真真,颜磊,张辉,张晓晖,赵兴波. 肿瘤微环境中TGF β-1对子宫内膜间质细胞活化的影响[J]. 山东大学学报（医学版）, 2016, 54(9): 37-40.
[6] 杨晖,董蓉,薛慧,胡祖权,曾柱. 肝癌细胞对人成熟树突状细胞影响的基因芯片分析[J]. 山东大学学报（医学版）, 2016, 54(1): 1-6.
[7] 陈海丽, 顾娇阳, 张文静, 袁琳冉, 郑娟, 袁中瑞. 经典Wnt信号通路在大鼠脑缺血后血管新生中的作用[J]. 山东大学学报（医学版）, 2015, 53(4): 31-36.
[8] 郑娟, 李政, 张文静, 袁琳冉, 樊书菠, 刘玉刚, 袁中瑞. Caveolin-1对脑缺血大鼠血管新生的影响[J]. 山东大学学报（医学版）, 2015, 53(10): 16-20.
[9] 陈少平, 王旬果, 郭燕春, 刘瑞宝, 王芳. 重组人血管内皮抑素在晚期消化道肿瘤化疗中的应用[J]. 山东大学学报（医学版）, 2014, 52(S1): 122-124.
[10] 屈福超，王爱红，孙永乐，王勇，苑海涛，张玉英. 瑞舒伐他汀改善大量饮酒对急性心肌梗死大鼠血管新生的影响[J]. 山东大学学报（医学版）, 2014, 52(4): 22-25.
[11] 贾颖，祖珊珊，郏雁飞，肖东杰，汪运山，马晓丽. CHRNA5基因表达下调对肺癌细胞VEGF表达的影响[J]. 山东大学学报（医学版）, 2014, 52(2): 12-15.
[12] 张淼慈, 李萍, 哈敏文. 重组人血管内皮抑素联合吉西他滨治疗铂类耐药复发卵巢癌的临床观察[J]. 山东大学学报（医学版）, 2014, 52(11): 55-59.
[13] 孙越,刘香岚,王群,郭春,石永玉,张利宁. 人TIPE家族新成员TIPE3特异性抗体的鉴定及应用[J]. 山东大学学报（医学版）, 2014, 52(1): 5-9.
[14] 张林1，侯艳红1，张健2，胡静1，张静1. 抗人EGFR/抗CD3双功能抗体治疗胰腺癌的实验研究[J]. 山东大学学报（医学版）, 2014, 52(1): 15-19.
[15] 祖珊珊1，马晓丽1,2，郏雁飞1,2，赵云3，贾颖1，肖东杰1,2，汪运山1,2. α5-烟碱型乙酰胆碱受体表达下调对肺癌细胞HIF-1α表达的影响[J]. 山东大学学报(医学版), 2013, 51(9): 8-12.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发