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Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System

机译:临床相关的辐射暴露有区别地影响先天和适应性免疫系统人类细胞中细胞死亡的形式

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摘要

In cancer treatments, especially high-dose radiotherapy (HDRT) is applied. Patients suffering from chronic inflammatory diseases benefit from low-dose radiation therapy (LDRT), but exposure to very low radiation doses can still steadily increase for diagnostic purposes. Yet, little is known about how radiation impacts on forms of cell death in human immune cells. In this study, the radiosensitivity of human immune cells of the peripheral blood was examined in a dose range from 0.01 to 60 Gy with regard to induction of apoptosis, primary necrosis, and secondary necrosis. Results showed that immune cells differed in their radiosensitivity, with monocytes being the most radioresistant. T cells mainly died by necrosis and were moderately radiosensitive. This was followed by B and natural killer (NK) cells, which died mainly by apoptosis. X-radiation had no impact on cell death in immune cells at very low doses (≤0.1 Gy). Radiation doses of LDRT (0.3–0.7 Gy) impacted on the more radiosensitive NK and B cells, which might contribute to attenuation of inflammation. Even single doses applied during RT of tumors did not erase the immune cells completely. These in vitro studies can be considered as the basis to optimize individual radiation therapy schemes in multimodal settings and to define suited time points for further inclusion of immunotherapies.
机译:在癌症治疗中,尤其是应用大剂量放射治疗(HDRT)。患有慢性炎性疾病的患者可从低剂量放射治疗(LDRT)中受益,但是出于诊断目的,暴露于非常低的放射剂量下仍可以稳定地增加。然而,关于辐射如何影响人类免疫细胞中细胞死亡形式的知之甚少。在这项研究中,在诱导凋亡,原发性坏死和继发性坏死的剂量范围为0.01至60 Gy的范围内检查了外周血人类免疫细胞的放射敏感性。结果显示免疫细胞的放射敏感性不同,单核细胞具有最高的放射抗性。 T细胞主要因坏死而死亡,对放射线具有中等敏感性。其次是B细胞和自然杀伤(NK)细胞,后者主要因凋亡而死亡。 X射线对非常低剂量(≤0.1Gy)的免疫细胞的细胞死亡没有影响。 LDRT的辐射剂量(0.3-0.7 Gy)影响到对放射线更敏感的NK和B细胞,这可能有助于减轻炎症。即使在肿瘤放疗期间单剂也不能完全清除免疫细胞。这些体外研究可被视为在多峰环境中优化单个放射治疗方案并为进一步纳入免疫疗法定义合适的时间点的基础。

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