文章：

基因编程诱导坏死性凋亡的人脂肪源性干细胞用于癌症免疫治疗

Human adipose-derived stem cells genetically programmed to induce necroptosis for cancer immunotherapy 

原文发布日期：2024-06-10 

英文摘要：

Herein, we present human adipose-derived stem cells (ADSCs) inserted with the receptor-interacting protein kinase-3 (RIP3) gene (RP@ADSCs), which induces cell necroptosis, for tumor immunotherapy. Necroptosis has characteristics of both apoptosis, such as programmed cell death, and necrosis, such as swelling and plasma membrane rupture, during which damage-related molecular patterns are released, triggering an immune response. Therefore, necroptosis has the potential to be used as an effective anticancer immunotherapy. RP@ADSCs were programmed to necroptosis after a particular time after being injected in vivo, and various pro-inflammatory cytokines secreted during the stem cell death process stimulated the immune system, showing local and sustained anticancer effects. It was confirmed that RIP3 protein expression increased in ADSCs after RP transfection. RP@ADSCs continued to induce ADSCs death for 7 days, and various pro-inflammatory cytokines were secreted through ADSCs death. The efficacy of RP@ADSCs-mediated immunotherapy was evaluated in mouse models bearing GL-26 (glioblastoma) and K1735 (melanoma), and it was found that RP resulted in an increase in the population of long-term cytotoxic T cells and a decrease in the population of regulatory T cells. This shows that RP@ADSCs have potential and applicability as an excellent anticancer immunotherapy agent in clinical practice. 

摘要翻译：

在此，我们提出将携带受体相互作用蛋白激酶3（RIP3）基因（RP@ADSCs）的人脂肪源性干细胞（ADSCs）用于肿瘤免疫治疗，该基因可诱导细胞坏死性凋亡。坏死性凋亡兼具程序性细胞死亡等凋亡特征以及细胞肿胀、质膜破裂等坏死特征，在此过程中会释放损伤相关分子模式，从而引发免疫反应。因此，坏死性凋亡有潜力成为一种有效的抗癌免疫疗法。RP@ADSCs在体内注射后特定时间被程序性诱导坏死性凋亡，干细胞死亡过程中分泌的各种促炎细胞因子刺激免疫系统，展现出局部且持续的抗癌效果。经证实，RP转染后ADSCs中RIP3蛋白表达量增加。RP@ADSCs持续诱导ADSCs死亡达7天，并通过ADSCs死亡分泌多种促炎细胞因子。在携带GL-26（胶质母细胞瘤）和K1735（黑色素瘤）的小鼠模型中评估RP@ADSCs介导的免疫治疗效果，发现RP导致长期细胞毒性T细胞群体增加而调节性T细胞群体减少。这表明RP@ADSCs在临床实践中具有作为优异抗癌免疫治疗剂的潜力与适用性。

原文链接：

Human adipose-derived stem cells genetically programmed to induce necroptosis for cancer immunotherapy