根據(jù)一項(xiàng)于2012年7月18日發(fā)表在Science Translational Medicine期刊上的研究，一類被稱作強(qiáng)心苷(cardiac glycosides)的心臟病藥物能夠誘導(dǎo)免疫原性細(xì)胞死亡(immunogenic cell death, ICD),，并以此將死亡的癌細(xì)胞轉(zhuǎn)化為一種刺激抗腫瘤反應(yīng)的疫苗。
來自法國國家健康與醫(yī)學(xué)研究院的Laurie Menger和同事們開發(fā)出并利用一種基于自動(dòng)化表面熒光顯微技術(shù)(epifluorescence microscopy)的平臺(tái)來鑒定免疫原性細(xì)胞死亡(ICD)的誘導(dǎo)劑,。
研究人員發(fā)現(xiàn)強(qiáng)心苷是一類強(qiáng)效的ICD誘導(dǎo)劑，而且這種效果與抑制細(xì)胞膜中的鈉鉀依賴性三磷酸腺苷酶相關(guān)聯(lián),。在具有免疫能力的小鼠體內(nèi),，它們的抗癌效果只有與DNA損傷性試劑一起使用時(shí)才能夠看得到,。經(jīng)過化療藥物和強(qiáng)心苷處理過的癌細(xì)胞能有效地作為經(jīng)過活的同類型癌細(xì)胞激發(fā)的小鼠的疫苗。此外,，對(duì)145名接受強(qiáng)心苷治療的癌癥患者和290名沒有接受強(qiáng)心苷治療的癌癥患者進(jìn)行的一項(xiàng)回顧性分析表明接受強(qiáng)心苷治療的患者5年存活率得到改善(風(fēng)險(xiǎn)比為0.62),。
Menger和同事們寫道，“確定一大類細(xì)胞毒性試劑擁有誘導(dǎo)ICD的能力將是令人感興趣的,，因此這有助于人們鑒定出引發(fā)一種免疫學(xué)上旁觀者效應(yīng)(bystander effect)的新藥物,。再者，在藥物開發(fā)生產(chǎn)線中,，基于它們促進(jìn)ICD的能力,，人們也可能明智地決定在臨床上開發(fā)出擁有相同靶標(biāo)和作物機(jī)制的化合物。”(生物谷：Bioon.com)
本文編譯自Heart medication converts cancer cells into vaccine
doi: 10.1126/scitranslmed.3003807
PMC:
PMID:
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.
