Nanobiotix, Paris, France.
Int J Nanomedicine. 2020 May 29;15:3843-3850. doi: 10.2147/IJN.S250490. eCollection 2020.
Despite tremendous results achieved by immune checkpoint inhibitors, most patients are not responders, mainly because of the lack of a pre-existing anti-tumor immune response. Thus, solutions to efficiently prime this immune response are currently under intensive investigations. Radiotherapy elicits cancer cell death, generating an antitumor-specific T cell response, turning tumors in personalized in situ vaccines, with potentially systemic effects (abscopal effect). Nonetheless, clinical evidence of sustained anti-tumor immunity as abscopal effect are rare.
Hafnium oxide nanoparticles (NBTXR3) have been designed to increase energy dose deposit within cancer cells. We examined the effect of radiotherapy-activated NBTXR3 on anti-tumor immune response activation and abscopal effect production using a mouse colorectal cancer model.
We demonstrate that radiotherapy-activated NBTXR3 kill more cancer cells than radiotherapy alone, significantly increase immune cell infiltrates both in treated and in untreated distant tumors, generating an abscopal effect dependent on CD8+ lymphocyte T cells.
These data show that radiotherapy-activated NBTXR3 could increase local and distant tumor control through immune system priming. Our results may have important implications for immunotherapeutic agent combination with radiotherapy.
尽管免疫检查点抑制剂取得了巨大的成果，但大多数患者并非应答者，主要是因为缺乏预先存在的抗肿瘤免疫反应。因此，目前正在深入研究有效引发这种免疫反应的解决方案。放射治疗会引发癌细胞死亡，产生针对肿瘤的特异性 T 细胞反应，使肿瘤变成个体化的原位疫苗，具有潜在的全身效应（远隔效应）。然而，远隔效应作为持续性抗肿瘤免疫的临床证据很少。
氧化铪纳米颗粒（NBTXR3）被设计用来增加癌细胞内的能量剂量沉积。我们使用小鼠结直肠癌细胞模型研究了放射治疗激活的 NBTXR3 对抗肿瘤免疫反应激活和远隔效应产生的影响。
我们证明，放射治疗激活的 NBTXR3 比单纯放射治疗杀死更多的癌细胞，显著增加治疗和未治疗的远处肿瘤中的免疫细胞浸润，产生依赖于 CD8+淋巴细胞 T 细胞的远隔效应。
这些数据表明，放射治疗激活的 NBTXR3 可以通过免疫系统的启动来增加局部和远处肿瘤的控制。我们的结果可能对免疫治疗药物与放射治疗的联合应用具有重要意义。
