Yang Yi, Lu Jing, Liu Hangfan, Jin Guoguo, Bai Ruihua, Li Xiang, Wang Dongyu, Zhao Jimin, Huang Youtian, Liu Kangdong, Xing Ying, Dong Ziming
Department of Pathophysiology, Basic Medical College, Zhengzhou University, No. 100 Science Road, Zhengzhou, 450001, Henan, People's Republic of China.
Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan, 450001, People's Republic of China.
Tumour Biol. 2016 Dec;37:15687–15695. doi: 10.1007/s13277-016-5312-7. Epub 2016 Oct 10.
Dendritic cells (DC) have been exploited for vaccination against cancer for years. DC loading autologous tumor lysate (ATL-DC) have been assessed in ongoing clinical trials, but frequently do not meet expectation. In this study, we found that mice immunized with ATL-DC induced less protective anti-tumor effect than immunized with DC alone. The percentage of CD8 T cells and the lysis efficiency of CTLs to auto tumor cells in ATL-DC vaccination group was less than that of DC group. Moreover, vaccination of mice with ATL-DC also promoted tumor angiogenesis by analyzing the CD31 positive microvessel density and hemoglobin content of tumor specimens. Human umbilical vein endothelial cells (HUVEC) have been proved effective in the anti-angiogenesis immunity against cancer. However, in the following research we found that the anti-tumor effect was attenuated while immunized mice with HUVEC combined with ATL-DC (HUVEC + ATL-DC). Furthermore, immunized mice with HUVEC + ATL-DC profoundly increased the tumor angiogenesis by analyzing the microvessel density and hemoglobin content of tumor specimens. These data suggest that vaccination using ATL-DC antagonized HUVEC induced anti-angiogenesis effect. Our research for the first time indicated that ATL-DC have the potential to promote the process of tumor angiogenesis in vivo. As vaccines based on DC loading autologous tumor lysate have been used in clinical, this find warned that the safety of this kind of vaccine should be taken into consideration seriously.
多年来，树突状细胞（DC）一直被用于癌症疫苗接种。负载自体肿瘤裂解物的DC（ATL-DC）已在正在进行的临床试验中进行了评估，但往往不尽人意。在本研究中，我们发现用ATL-DC免疫的小鼠诱导的保护性抗肿瘤作用比单独用DC免疫的小鼠要小。ATL-DC疫苗接种组中CD8 T细胞的百分比和CTL对自体肿瘤细胞的裂解效率低于DC组。此外，通过分析肿瘤标本的CD31阳性微血管密度和血红蛋白含量，发现用ATL-DC对小鼠进行疫苗接种也促进了肿瘤血管生成。人脐静脉内皮细胞（HUVEC）已被证明在抗癌血管生成免疫中有效。然而，在接下来的研究中，我们发现用HUVEC与ATL-DC联合免疫小鼠（HUVEC + ATL-DC）时，抗肿瘤作用减弱。此外，通过分析肿瘤标本的微血管密度和血红蛋白含量，发现用HUVEC + ATL-DC免疫的小鼠显著增加了肿瘤血管生成。这些数据表明，使用ATL-DC进行疫苗接种会拮抗HUVEC诱导的抗血管生成作用。我们的研究首次表明，ATL-DC在体内有促进肿瘤血管生成过程的潜力。由于基于负载自体肿瘤裂解物的DC疫苗已在临床上使用，这一发现警示应认真考虑这类疫苗的安全性。
