Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts; Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Radiology, Harvard Medical School, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2023 Jul 15;116(4):906-915. doi: 10.1016/j.ijrobp.2022.12.051. Epub 2023 May 16.
The aim of this work was to determine whether intratumoral injections of a liquid oxygen solution are effective at boosting radiation-induced abscopal effects.
A liquid oxygen solution, comprising slow-release polymer-shelled oxygen microparticles, was fabricated and injected intratumorally to locally elevate tumor oxygen levels before and after treatment with radiation therapy. Changes in tumor volume were monitored. In a subset of studies, CD8-positive cells were depleted and the experiments were repeated. Histologic analyses of the tumor tissues were performed to quantify the concentration of infiltrating immune cells.
Daily intratumoral injections of oxygen-filled microparticles significantly retarded primary and secondary tumor growth, boosted infiltration of cytotoxic T cells, and improved overall survival when used as an adjuvant to radiation therapy. The findings also demonstrated that efficacy requires both radiation and oxygen, suggesting that they act synergistically to enhance in situ vaccination and systemic antitumor immune responses.
This study demonstrated the potential advantages of intratumoral injections of a liquid oxygen solution as a strategy to boost radiation-induced abscopal effects, and the findings warrant future efforts toward clinical translation of the injectable liquid oxygen solution.
本研究旨在确定瘤内注射液态氧溶液是否能有效增强放射治疗的远隔效应。
制备了一种液态氧溶液，由缓释聚合物壳氧微球组成，在放射治疗前后瘤内注射以局部提高肿瘤氧水平。监测肿瘤体积的变化。在部分研究中，耗尽 CD8 阳性细胞并重复实验。对肿瘤组织进行组织学分析，以定量浸润免疫细胞的浓度。
每日瘤内注射充氧微球可显著延缓原发和继发肿瘤的生长，增强细胞毒性 T 细胞的浸润，并改善整体生存率，作为放射治疗的辅助手段。研究结果还表明，疗效需要辐射和氧气的共同作用，这表明它们协同作用以增强原位疫苗接种和全身抗肿瘤免疫反应。
本研究证明了瘤内注射液态氧溶液作为增强放射治疗远隔效应的策略的潜在优势，这一发现值得进一步努力将可注射液态氧溶液推向临床应用。
