The Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences, Lund University, Lund, Sweden.
Medical Radiation Physics, Department of Clinical Sciences, Lund University, Lund, Sweden.
Sci Rep. 2022 Jul 19;12(1):12285. doi: 10.1038/s41598-022-16612-6.
Radiotherapy can induce an immunological response. One limiting factor is side effects on normal tissue. Using FLASH radiotherapy, side effects could possibly be reduced. The efficacy of FLASH in relation to conventional radiotherapy (CONV-RT) has not been extensively explored in fully immunocompetent animals. Fully immunocompetent Fischer 344 rats were inoculated with NS1 glioblastoma cells subcutaneously or intracranially. Radiotherapy was delivered with FLASH or CONV-RT at 8 Gy × 2 (subcutaneous tumors) and 12.5 Gy × 2 (intracranial tumors). Cured animals were re-challenged in order to explore long-term anti-tumor immunity. Serum analytes and gene expression were explored. The majority of animals with subcutaneous tumors were cured when treated with FLASH or CONV-RT at 8 Gy × 2. Cured animals could reject tumor re-challenge. TIMP-1 in serum was reduced in animals treated with FLASH 8 Gy × 2 compared to control animals. Animals with intracranial tumors survived longer when treated with FLASH or CONV-RT at 12.5 Gy × 2, but cure was not reached. CONV-RT and FLASH were equally effective in fully immunocompetent animals with glioblastoma. Radiotherapy was highly efficient in the subcutaneous setting, leading to cure and long-term immunity in the majority of the animals.
放射治疗可以诱导免疫反应。一个限制因素是对正常组织的副作用。使用 FLASH 放射治疗，副作用可能会减少。FLASH 在完全免疫功能正常的动物中与常规放射治疗（CONV-RT）的疗效尚未得到广泛探索。完全免疫功能正常的 Fischer 344 大鼠皮下或颅内接种 NS1 神经胶质瘤细胞。FLASH 或 CONV-RT 以 8 Gy×2（皮下肿瘤）和 12.5 Gy×2（颅内肿瘤）进行放射治疗。治愈的动物被重新挑战，以探索长期抗肿瘤免疫。探索血清分析物和基因表达。当用 FLASH 或 CONV-RT 以 8 Gy×2 治疗时，大多数患有皮下肿瘤的动物被治愈。治愈的动物可以拒绝肿瘤再挑战。与对照动物相比，用 FLASH 8 Gy×2 治疗的动物血清中 TIMP-1 减少。当用 FLASH 或 CONV-RT 以 12.5 Gy×2 治疗时，颅内肿瘤的动物存活时间更长，但未达到治愈。FLASH 和 CONV-RT 在完全免疫功能正常的神经胶质瘤动物中同样有效。放射治疗在皮下环境中非常有效，导致大多数动物治愈和长期免疫。
