血管内皮抑素协同肿瘤特异性DC-T细胞的抗肿瘤效应

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

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(m DC)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m DC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。

Objective To investigate the antitumor effect of endostatin combined with tumor special DC-T cellular therapy on lung cancer in Lew is mice. Methods C57 BL /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 M DSC,TAM（ M1 / M2）,m DC 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 M DSC and TAM（ M2 type） were reduced,while proportions of m DC,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.