Improved Antitumor Efficacy of Combined Vaccine Based on the Induced HUVECs and DC-CT26 Against Colorectal Carcinoma
Improved Antitumor Efficacy of Combined Vaccine Based on the Induced HUVECs and DC-CT26 Against Colorectal Carcinoma
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基于诱导 HUVEC 和 DC-CT26 的联合疫苗抗结直肠癌的抗肿瘤效果提高
DOI：
10.3390/cells8050494
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发表时间：
2019-05-01
期刊：
影响因子：
6
通讯作者：
Lu, Jing
中科院分区：
文献类型：
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作者：
Zhang, Qiushuang;Xie, Chao;Lu, Jing
血管生成对于实体瘤的发展、生长和转移是必不可少的。用活的人脐静脉内皮细胞（HUVECs）接种已用于抗肿瘤血管生成。然而，HUVECs诱导的有限免疫应答阻碍了其临床应用。在本研究中，我们发现，由肿瘤微环境诱导的HUVECs使用小鼠CT 26结直肠癌细胞的上清液比HUVECs本身发挥更好的抗血管生成作用。诱导HUVEC组对肿瘤生长的抑制作用明显优于HUVEC组，且诱导HUVEC组对肿瘤组织中CD 31阳性微血管密度表现出较强的抑制作用。此外，小鼠血清中抗诱导的HUVEC膜蛋白抗体水平在诱导的HUVEC组中显著高于HUVEC组。基于此，评价了具有诱导的HUVEC和负载树突状细胞的CT 26抗原（DC-CT 26）的组合的疫苗的抗肿瘤效果。值得注意的是，联合疫苗组中肿瘤标本的微血管密度显著低于对照组。联合疫苗组脾脏指数、细胞毒性T淋巴细胞（CTL）杀伤效应和血清γ-干扰素浓度均显著提高。基于这些结果，靶向肿瘤血管生成和肿瘤细胞的联合疫苗可能是一种有吸引力的和有效的癌症免疫治疗策略。
Angiogenesis is essential for the development, growth, and metastasis of solid tumors. Vaccination with viable human umbilical vein endothelial cells (HUVECs) has been used for antitumor angiogenesis. However, the limited immune response induced by HUVECs hinders their clinical application. In the present study, we found that HUVECs induced by a tumor microenvironment using the supernatant of murine CT26 colorectal cancer cells exerted a better antiangiogenic effect than HUVECs themselves. The inhibitory effect on tumor growth in the induced HUVEC group was significantly better than that of the HUVEC group, and the induced HUVEC group showed a strong inhibition in CD31-positive microvessel density in the tumor tissues. Moreover, the level of anti-induced HUVEC membrane protein antibody in mouse serum was profoundly higher in the induced HUVEC group than in the HUVEC group. Based on this, the antitumor effect of a vaccine with a combination of induced HUVECs and dendritic cell-loading CT26 antigen (DC-CT26) was evaluated. Notably, the microvessel density of tumor specimens was significantly lower in the combined vaccine group than in the control groups. Furthermore, the spleen index, the killing effect of cytotoxic T lymphocytes (CTLs), and the concentration of interferon-γ in the serum were enhanced in the combined vaccine group. Based on these results, the combined vaccine targeting both tumor angiogenesis and tumor cells may be an attractive and effective cancer immunotherapy strategy.