Sci Transl Med：心脏病药物将癌细胞转化为疫苗

根据一项于2012年7月18日发表在Science Translational Medicine期刊上的研究，一类被称作强心苷(cardiac glycosides)的心脏病药物能够诱导免疫原性细胞死亡(immunogenic cell death, ICD)，并以此将死亡的癌细胞转化为一种刺激抗肿瘤反应的疫苗。

来自法国国家健康与医学研究院的Laurie Menger和同事们开发出并利用一种基于自动化表面荧光显微技术(epifluorescence microscopy)的平台来鉴定免疫原性细胞死亡(ICD)的诱导剂。

研究人员发现强心苷是一类强效的ICD诱导剂，而且这种效果与抑制细胞膜中的钠钾依赖性三磷酸腺苷酶相关联。在具有免疫能力的小鼠体内，它们的抗癌效果只有与DNA损伤性试剂一起使用时才能够看得到。经过化疗药物和强心苷处理过的癌细胞能有效地作为经过活的同类型癌细胞激发的小鼠的疫苗。此外，对145名接受强心苷治疗的癌症患者和290名没有接受强心苷治疗的癌症患者进行的一项回顾性分析表明接受强心苷治疗的患者5年存活率得到改善(风险比为0.62)。

Menger和同事们写道，“确定一大类细胞毒性试剂拥有诱导ICD的能力将是令人感兴趣的，因此这有助于人们鉴定出引发一种免疫学上旁观者效应(bystander effect)的新药物。再者，在药物开发生产线中，基于它们促进ICD的能力，人们也可能明智地决定在临床上开发出拥有相同靶标和作物机制的化合物。”

本文编译自Heart medication converts cancer cells into vaccine

doi: 10.1126/scitranslmed.3003807
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Cardiac Glycosides Exert Anticancer Effects by Inducing Immunogenic Cell Death

Laurie Menger1,2,3, Erika Vacchelli1,2,3, Sandy Adjemian et al.

Some successful chemotherapeutics, notably anthracyclines and oxaliplatin, induce a type of cell stress and death that is immunogenic, hence converting the patient’s dying cancer cells into a vaccine that stimulates antitumor immune responses. By means of a fluorescence microscopy platform that allows for the automated detection of the biochemical hallmarks of such a peculiar cell death modality, we identified cardiac glycosides (CGs) as exceptionally efficient inducers of immunogenic cell death, an effect that was associated with the inhibition of the plasma membrane Na+- and K+-dependent adenosine triphosphatase (Na+/K+-ATPase). CGs exacerbated the antineoplastic effects of DNA-damaging agents in immunocompetent but not immunodeficient mice. Moreover, cancer cells succumbing to a combination of chemotherapy plus CGs could vaccinate syngeneic mice against a subsequent challenge with living cells of the same type. Finally, retrospective clinical analyses revealed that the administration of the CG digoxin during chemotherapy had a positive impact on overall survival in cohorts of breast, colorectal, head and neck, and hepatocellular carcinoma patients, especially when they were treated with agents other than anthracyclines and oxaliplatin.