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临床相关辐射暴露对固有和适应性免疫系统人类细胞的细胞死亡形式有不同影响。

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

机构信息

Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

出版信息

Int J Mol Sci. 2018 Nov 13;19(11):3574. doi: 10.3390/ijms19113574.

Abstract

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.

摘要

在癌症治疗中,特别是应用高剂量放疗(HDRT)。患有慢性炎症性疾病的患者受益于低剂量辐射治疗(LDRT),但为了诊断目的,极低剂量的辐射仍会持续增加。然而,人们对辐射如何影响人类免疫细胞的死亡形式知之甚少。在这项研究中,研究了外周血免疫细胞在 0.01 至 60 Gy 的剂量范围内对凋亡、原发性坏死和继发性坏死的诱导的放射敏感性。结果表明,免疫细胞的放射敏感性不同,单核细胞的放射抗性最强。T 细胞主要通过坏死而死亡,并且具有中度放射敏感性。其次是 B 细胞和自然杀伤(NK)细胞,它们主要通过凋亡而死亡。X 射线在非常低的剂量(≤0.1 Gy)下对免疫细胞的细胞死亡没有影响。LDRT(0.3⁻0.7 Gy)的辐射剂量会影响更敏感的 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次应用剂量,也不会完全消除免疫细胞。这些体外研究可以被认为是在多模式环境中优化个体放疗方案和确定适合免疫治疗进一步纳入的时间点的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1b6/6274975/533eabc04450/ijms-19-03574-g001.jpg

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