Abstract

Objective

The goal of this study is to better understand the immunogenetic expression and related cytotoxic responses of moderate but clinically relevant doses of hypofractionated radiation (1x15 Gy and 3x8 Gy) and magnetic nanoparticle hyperthermia (mNPH, CEM43 30)

Methods

Genetic, protein, immunopathology and tumor growth delay assessments were used to determine the immune and cytotoxic responses following radiation and mNPH alone and in combination. Although the thermal dose used, 43 C°/30 min (CEM43 30), typically results in modest independent cytotoxicity, it has shown the ability to stimulate an immune response and enhance other cancer treatments. The radiation doses studied (15 Gy and 3x8 Gy) are commonly used in preclinical research and are effective in selected stereotactic and palliative treatment settings, however they are not commonly used as first-line primary tumor treatment regimens.

Results

Our RNA-based genetic results suggest that while many of the cytotoxic and immune gene and protein pathways for radiation and hyperthermia are similar, radiation, at the doses used, results in a more consistent and expansive anti-cancer immune/cytotoxic expression profile. These results were supported by immunohistochemistry based cytotoxic T-cell tumor infiltration and tumor growth delay studies. When used together radiation and hyperthermia led to greater immune and cytotoxic activity than either modality alone.

Conclusion

This study clearly shows that modest, but commonly used hypofractionated radiation and hyperthermia doses share many important immune and cytotoxic pathways and that combining the treatments, as compared to either treatment alone, results in genetic and biological anti-cancer benefits.

中文翻译：

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mNP 热疗和大分割放射激活类似的免疫遗传和细胞毒性途径。

 抽象的

 客观的

本研究的目的是更好地了解中等但临床相关剂量的大分割放射（1x15 Gy 和 3x8 Gy）和磁性纳米颗粒热疗（mNPH、CEM43 30）的免疫遗传学表达和相关细胞毒性反应

 方法

遗传、蛋白质、免疫病理学和肿瘤生长延迟评估用于确定单独或组合放射和 mNPH 后的免疫和细胞毒性反应。尽管使用的热剂量 43 C°/30 分钟 (CEM43 30) 通常会产生适度的独立细胞毒性，但它已显示出刺激免疫反应和增强其他癌症治疗的能力。研究的放射剂量（15 Gy 和 3x8 Gy）常用于临床前研究，并且在选定的立体定向和姑息治疗环境中有效，但它们通常不用作一线原发性肿瘤治疗方案。

 结果

我们基于 RNA 的遗传学结果表明，虽然辐射和热疗的许多细胞毒性和免疫基因和蛋白质途径相似，但所用剂量的辐射会产生更一致和更广泛的抗癌免疫/细胞毒性表达谱。这些结果得到了基于免疫组织化学的细胞毒性 T 细胞肿瘤浸润和肿瘤生长延迟研究的支持。当放疗和热疗一起使用时，比单独使用任何一种方式产生更大的免疫和细胞毒性活性。

 结论

这项研究清楚地表明，适度但常用的大分割放射和热疗剂量具有许多重要的免疫和细胞毒性途径，并且与单独治疗相比，联合治疗可产生遗传和生物抗癌益处。