Burgdorf Stefan K, Claesson Mogens H, Nielsen Hans J, Rosenberg Jacob
Department of Surgical Gastroenterology, Herlev Hospital, University of Copenhagen, Denmark.
Acta Oncol. 2009;48(8):1157-64. doi: 10.3109/02841860903099964.
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 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.
引言。基于树突状细胞疫苗接种的免疫疗法在癌症治疗方面有着令人兴奋的前景。为了阐明疫苗接种过程中的免疫机制，对反应进行密集监测至关重要。这可能会带来治疗的优化以及对有反应患者的预测。本研究的目的是评估用基于同种异体黑色素瘤细胞裂解物脉冲处理的树突状细胞癌症疫苗治疗的结直肠癌患者的细胞因子和生物标志物反应。材料与方法。在接种疫苗前以及治疗期间持续采集血浆和血清样本。使用Luminex 100仪器通过多重检测法分析GM-CSF、IL-2、IL-6、TNF-α、IFN-γ、IL-4、IL-8、IL-1β、IL-5、IL-10、IL-12、MIP-1β、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。病情稳定的患者血浆GM-CSF、TNF-α、IFN-γ、IL-2和IL-5水平升高。病情进展的患者CEA和TIMP-1水平显著升高，而病情稳定的患者水平相对未改变。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Th1反应。由于Th1反应似乎在癌症免疫治疗中至关重要，这可能表明该疫苗具有治疗潜力。
