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光动力疗法生成的癌症疫苗可引发治疗小鼠的急性期和激素反应。

Photodynamic therapy-generated cancer vaccine elicits acute phase and hormonal response in treated mice.

机构信息

British Columbia Cancer Agency, BC Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada.

出版信息

Cancer Immunol Immunother. 2012 Sep;61(9):1387-94. doi: 10.1007/s00262-012-1206-8. Epub 2012 Jan 24.

Abstract

Photodynamic therapy (PDT)-generated cancer vaccines have shown promising results in preclinical studies and are being introduced in the clinics. Using an SCCVII mouse squamous cell carcinoma-based whole-cell autologous PDT vaccine model developed in our previous work, we have examined systemic effects in vaccinated mice that could be related to the induction of acute phase response. The upregulation of gene encoding serum amyloid P component (prototypic mouse acute phase reactant) was detected in the liver and to a lesser degree in the tumor of vaccinated mice at 24 h post-PDT vaccine treatment. A strong upregulation of gene for heat shock protein 70 was found in both the liver and tumor of mice at 4 h after their PDT vaccine treatment. Changes in the expression of genes for glucocorticoid-induced leucine zipper and serum- and glucocorticoid-regulated kinase 1 that are highly responsive to glucocorticoid modulation were uncovered in both the tumor and liver of vaccinated mice. A rise in the levels of serum corticosterone was detected in mice at 24 h after PDT vaccine treatment. The results indicate that a sudden appearance of a large number of PDT vaccine cells elicits host responses for securing their optimized clearance, which in addition to producing seminal acute phase reactants includes the engagement of glucocorticoid hormones. It is becoming increasingly clear that a consummate execution of this process of PDT vaccine cell removal is critical for tumor antigen recognition and the attainment of potent antitumor immune response.

摘要

光动力疗法 (PDT) 生成的癌症疫苗在临床前研究中显示出有希望的结果,并正在引入临床。在我们之前的工作中,使用 SCCVII 小鼠鳞状细胞癌全细胞自体 PDT 疫苗模型,我们研究了接种疫苗的小鼠中的全身效应,这些效应可能与诱导急性期反应有关。在 PDT 疫苗治疗后 24 小时,在接种疫苗的小鼠的肝脏中检测到编码血清淀粉样蛋白 P 成分(典型的小鼠急性期反应物)的基因上调,在肿瘤中则较少。在 PDT 疫苗治疗后 4 小时,在小鼠的肝脏和肿瘤中均发现热休克蛋白 70 的基因强烈上调。在接种疫苗的小鼠的肿瘤和肝脏中发现了糖皮质激素诱导的亮氨酸拉链和血清和糖皮质激素调节激酶 1 的基因表达发生变化,这些基因对糖皮质激素调节高度敏感。在 PDT 疫苗治疗后 24 小时,检测到小鼠血清皮质酮水平升高。结果表明,大量突然出现的 PDT 疫苗细胞会引发宿主反应,以确保其最佳清除,除了产生主要的急性期反应物外,还包括糖皮质激素的参与。越来越明显的是,这种 PDT 疫苗细胞清除过程的完美执行对于肿瘤抗原识别和获得有效的抗肿瘤免疫反应至关重要。

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