Department of Radiation Oncology, Samsung Medical Center, Seoul 06351, Korea.
Department of Medicine, Samsung Medical Center, Sungkyunwan University School of Medicine, Seoul 06351, Korea.
Int J Mol Sci. 2021 Mar 5;22(5):2637. doi: 10.3390/ijms22052637.
We evaluated the effect of manganese ferrite nanoparticles (MFN) on radiosensitization and immunologic responses using the murine hepatoma cell line Hepa1-6 and the syngeneic mouse model. The clonogenic survival of Hepa1-6 cells was increased by hypoxia, while being restricted by ionizing radiation (IR) and/or MFN. Although MFN suppressed HIF-1α under hypoxia, the combination of IR and MFN enhanced apoptosis and DNA damage in Hepa1-6 cells. In the Hepa1-6 syngeneic mouse model, the combination of IR and MFN notably limited the tumor growth compared to the single treatment with IR or MFN, and also triggered more frequent apoptosis in tumor tissues than that observed under other conditions. Increased expression of PD-L1 after IR was not observed with MFN alone or the combination of IR and MFN in vitro and in vivo, and the percentage of tumor-infiltrating T cells and cytotoxic T cells increased with MFN, regardless of IR, in the Hepa1-6 syngeneic mouse model, while IR alone led to T cell depletion. MFN might have the potential to overcome radioresistance by alleviating hypoxia and strengthening antitumor immunity in the tumor microenvironment.
我们使用小鼠肝癌细胞系 Hepa1-6 及同基因小鼠模型评估了锰铁氧体纳米颗粒 (MFN) 对放射增敏和免疫反应的影响。缺氧会增加 Hepa1-6 细胞的克隆存活能力，而电离辐射 (IR) 和/或 MFN 则会限制其存活。尽管 MFN 在低氧条件下抑制了 HIF-1α，但 IR 和 MFN 的联合作用增强了 Hepa1-6 细胞的凋亡和 DNA 损伤。在 Hepa1-6 同基因小鼠模型中，与单独使用 IR 或 MFN 相比，IR 和 MFN 的联合治疗显著限制了肿瘤生长，并且在肿瘤组织中引发的凋亡也比其他情况下更为频繁。在体外和体内，IR 单独或与 IR 和 MFN 联合使用均不会导致 MFN 单独或联合使用时 PD-L1 的表达增加，并且无论是否使用 IR，MFN 均可增加肿瘤浸润 T 细胞和细胞毒性 T 细胞的百分比，而 IR 单独使用则会导致 T 细胞耗竭。MFN 可能通过减轻肿瘤微环境中的缺氧并增强抗肿瘤免疫来克服放射抵抗。
