Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia "Seràgnoli", Università degli Studi, 40138 Bologna, Italy.
Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, 40138 Bologna, Italy.
Int J Mol Sci. 2020 Sep 16;21(18):6802. doi: 10.3390/ijms21186802.
Recent evidence demonstrated that the treatment of acute myeloid leukemia (AML) cells with daunorubicin (DNR) but not cytarabine (Ara-C) results in immunogenic cell death (ICD). In the clinical setting, chemotherapy including anthracyclines and Ara-C remains a gold standard for AML treatment. In the last decade, etoposide (Eto) and fludarabine (Flu) have been added to the standard treatment for AML to potentiate its therapeutic effect and have been tested in many trials. Very little data are available about the ability of these drugs to induce ICD.
AML cells were treated with all four drugs. Calreticulin and heat shock protein 70/90 translocation, non-histone chromatin-binding protein high mobility group box 1 and adenosine triphosphate release were evaluated. The treated cells were pulsed into dendritic cells (DCs) and used for in vitro immunological tests.
Flu and Ara-C had no capacity to induce ICD-related events. Interestingly, Eto was comparable to DNR in inducing all ICD events, resulting in DC maturation. Moreover, Flu was significantly more potent in inducing suppressive T regulatory cells compared to other drugs.
Our results indicate a novel and until now poorly investigated feature of antineoplastic drugs commonly used for AML treatment, based on their different immunogenic potential.
最近的证据表明，用柔红霉素（DNR）而不是阿糖胞苷（Ara-C）治疗急性髓细胞白血病（AML）细胞会导致免疫原性细胞死亡（ICD）。在临床环境中，包括蒽环类药物和 Ara-C 的化疗仍然是 AML 治疗的金标准。在过去的十年中，依托泊苷（Eto）和氟达拉滨（Flu）已被添加到 AML 的标准治疗中，以增强其治疗效果，并在许多试验中进行了测试。关于这些药物诱导 ICD 的能力的数据非常有限。
用所有四种药物处理 AML 细胞。评估钙网蛋白和热休克蛋白 70/90 易位、非组蛋白染色质结合蛋白高迁移率族框 1 和三磷酸腺苷释放。处理后的细胞被脉冲进入树突状细胞（DC）并用于体外免疫测试。
Flu 和 Ara-C 没有诱导 ICD 相关事件的能力。有趣的是，Eto 与 DNR 相当，可诱导所有 ICD 事件，导致 DC 成熟。此外，与其他药物相比，Flu 更能诱导抑制性 T 调节细胞。
我们的结果表明，基于其不同的免疫原性潜力，常用的 AML 治疗抗肿瘤药物具有一种新的、迄今为止研究甚少的特征。
