Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination
Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination
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DOI：
10.3109/02841860903099964
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发表时间：
2009-01-01
期刊：
影响因子：
3.1
通讯作者：
Rosenberg, Jacob
中科院分区：
文献类型：
--
作者：
Burgdorf, Stefan K.;Claesson, Mogens H.;Rosenberg, Jacob
导论.基于树突状细胞疫苗接种的免疫疗法对于癌症的治疗具有令人兴奋的前景。为了阐明疫苗接种期间的免疫机制，必须密切监测反应。这可能导致治疗的优化和响应患者的预测。本研究的目的是评估细胞因子和生物标志物的反应与癌症疫苗治疗的结直肠癌患者的树突状细胞脉冲与同种异体黑色素瘤细胞裂解物的基础上。材料和方法。在疫苗接种前和治疗期间连续采集血浆和血清样本。在使用Luminex 100（TM）仪器的多重测定中分析GM-CSF、IL-2、IL-6、TNF-α、IFN-γ、IL-4、IL-8、IL-1b、IL-5、IL-10、IL-12、MIP-1b、IP-10和嗜酸性粒细胞趋化因子。在ELISA平台上分析CEA和TIMP-1。结果达到稳定疾病的患者显示血浆GM-CSF、TNF-α、IFN-γ、IL-2和IL-5水平升高。进展性疾病患者的CEA和TIMP-1水平显著升高，而稳定性疾病患者的水平相对不变。结论接种疫苗后病情稳定的患者血清中关键促炎细胞因子水平升高，表明发生了疫苗诱导的Th 1应答。由于Th 1应答似乎在癌症免疫治疗中是必不可少的，这可能表明疫苗的治疗潜力。
Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior to vaccination and continuously during treatment. GM-CSF, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-4, IL-8, IL-1b, IL-5, IL-10, IL-12, MIP-1b, IP-10 and Eotaxin were analyzed in a multiplex assay with a Luminex 100 (TM) instrument. CEA and TIMP-1 were analysed on ELISA platforms. Results. Patients achieving stable disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. Conclusion. The increased levels of key pro-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine.