Low-dose docetaxel enhances the anti-tumour efficacy of a human umbilical vein endothelial cell vaccine
Low-dose docetaxel enhances the anti-tumour efficacy of a human umbilical vein endothelial cell vaccine
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小剂量多西他赛增强人脐静脉内皮细胞疫苗的抗肿瘤功效
DOI：
10.1016/j.ejps.2019.105163
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发表时间：
2020
影响因子：
4.6
通讯作者：
Xu Maolei
中科院分区：
文献类型：
--
作者：
Zhou Ling;Lu Meiyu;Zhong Weilan;Yang Junhou;Yin Yancun;Li Minjing;Li Defang;Zhang Shumin;Xu Maolei
我们以前的研究表明，人脐静脉内皮细胞(HUVEC)疫苗似乎是一种潜在的抗血管生成疗法，但适度的抗肿瘤疗效限制了其临床应用。这突出了确定更有效的治疗性HUVEC疫苗策略用于临床测试的重要性。本研究将免疫调节剂量的多西紫杉醇(DOC)与1×106个活的人脐静脉内皮细胞(HUVEC)相结合，以提高HUVEC疫苗的治疗抗肿瘤效率。我们的结果表明，在HUVEC疫苗之前给予5 mg/kg DOC可以最有效地辅助HUVEC疫苗在治疗过程中显示出显着的抑制肿瘤生长和转移以及延长生存时间的作用。切除肿瘤的CD31免疫组织化学分析证实，在使用含5 mg/kg DOC的HUVEC疫苗治疗后，血管密度显著降低。此外，经5 mg/kgDOC处理的人脐静脉内皮细胞疫苗处理后，脾细胞特异性抗体水平、活化的CTL和干扰素-γ水平均升高。最后，5 mg/kg DOC联合HUVEC疫苗可诱导肿瘤微环境中CD8+T细胞显著增加，Tregs减少。综上所述，5 mg/kg DOC可帮助HUVEC疫苗诱导出较强的HUVEC特异性体液和细胞免疫应答，从而促进HUVEC疫苗介导的抑制肿瘤生长和转移。这些发现为癌症患者联合使用免疫调节剂DOC和HUVEC疫苗提供了免疫学基础。
Our previous studies have indicated that human umbilical vein endothelial cell (HUVEC) vaccination appears to be a potentially promising anti-angiogenesis therapy, but the modest therapeutic anti-tumour efficiency limits its clinical use. This highlights the importance of identifying more potent therapeutic HUVEC vaccine strategies for clinical testing. In the present study, the immune-modulating doses of docetaxel (DOC) was combined with 1 × 106viable HUVECs as a means to enhance the therapeutic anti-tumour efficiency of the HUVEC vaccine. Our results demonstrated that 5 mg/kg DOC administrated prior to HUVEC vaccine could most effectively assist HUVEC vaccine to display a remarkable suppression of tumour growth and metastasis as wells as a prolongation of survival time in a therapeutic procedure. CD31 immunohistochemical analysis of the excised tumours confirmed a significant reduction in vessel density after treatment with the HUVEC vaccine with 5 mg/kg DOC. Additionally, an increased HUVEC-specific antibody level, activated CTLs and an elevated IFN-γ level in cultured splenocytes were revealed after treatment with HUVEC vaccine with 5 mg/kg DOC. Finally, 5 mg/kg DOC coupled with the HUVEC vaccine led to induction of significant increases in CD8+Tcells and decrease in Tregs in the tumour microenvironment. Taken together, all the results verified that 5 mg/kg DOC could assist HUVEC vaccine to elicit strong HUVEC specific humoral and cellular responses, which could facilitate the HUVEC vaccine-mediated inhibition of cancer growth and metastasis. These findings provide the immunological rationale for the combined use of immune-modulating doses of DOC and HUVEC vaccines in patients with cancer.