Pandey J P, Kistner-Griffin E, Namboodiri A M, Iwasaki M, Kasuga Y, Hamada G S, Tsugane S
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
Clin Exp Immunol. 2014 Oct;178(1):75-8. doi: 10.1111/cei.12385.
Cyclin B1 is a checkpoint protein that regulates cell division from G2 to the M phase. Studies in mice have shown that cyclin B1 vaccine-induced immunity significantly delayed or prevented the spontaneous cancer development later in life. We hypothesized that if these results showing a protective effect of anti-cyclin B1 antibodies could be extrapolated to the human condition, cancer-free individuals should have higher levels of endogenous antibodies than patients with cancers characterized by the over-expression of this tumour-associated antigen. To test this hypothesis, we characterized a large (1739 subjects) number of multi-ethnic patients with breast cancer (which over-expresses cyclin B1) and matched controls for anti-cyclin B1 immunoglobulin (Ig)G antibodies. Multivariate analyses, after adjusting for the covariates, showed that cancer-free individuals had significantly higher levels of naturally occurring IgG antibodies to cyclin B1 than patients with breast cancer (mean ± standard deviation: 148·0 ± 73·6 versus 126·1 ± 67·8 arbitrary units per ml; P < 0·0001). These findings may have important implications for cyclin B1-based immunotherapy against breast cancer and many other cyclin B1-over-expressing malignancies.
细胞周期蛋白B1是一种检查点蛋白,可调节从G2期到M期的细胞分裂。对小鼠的研究表明,细胞周期蛋白B1疫苗诱导的免疫显著延迟或预防了后期的自发性癌症发展。我们推测,如果这些显示抗细胞周期蛋白B1抗体具有保护作用的结果能够外推至人类情况,那么无癌个体应比以这种肿瘤相关抗原过度表达为特征的癌症患者具有更高水平的内源性抗体。为了验证这一假设,我们对大量(1739名受试者)多民族乳腺癌患者(其细胞周期蛋白B1过度表达)及相匹配的对照者的抗细胞周期蛋白B1免疫球蛋白(Ig)G抗体进行了特征分析。在对协变量进行校正后的多变量分析显示,无癌个体针对细胞周期蛋白B1的天然存在的IgG抗体水平显著高于乳腺癌患者(平均值±标准差:每毫升148.0±73.6与126.1±67.8任意单位;P<0.0001)。这些发现可能对基于细胞周期蛋白B1的乳腺癌及许多其他细胞周期蛋白B1过度表达的恶性肿瘤的免疫治疗具有重要意义。