Validating the pivotal role of the immune system in low-dose radiation-induced tumor inhibition in Lewis lung cancer-bearing mice.
Validating the pivotal role of the immune system in low-dose radiation-induced tumor inhibition in Lewis lung cancer-bearing mice.
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验证免疫系统在 Lewis 肺癌小鼠低剂量辐射诱导的肿瘤抑制中的关键作用
DOI：
10.1002/cam4.1344
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发表时间：
2018-04
期刊：
影响因子：
4
通讯作者：
Cui J
中科院分区：
文献类型：
--
作者：
Zhou L;Zhang X;Li H;Niu C;Yu D;Yang G;Liang X;Wen X;Li M;Cui J
虽然低剂量辐射(LDR)具有诱导兴奋和适应性反应两种不同的功能，从而导致免疫增强和肿瘤抑制，但其临床应用尚未阐明。阻碍LDR在临床应用的主要障碍是诱导肿瘤抑制的潜在机制尚不清楚，与LDR相关的风险也尚不清楚。因此，为了克服这一障碍，并阐明LDR抗肿瘤作用的机制，本研究建立了体内肺癌模型，探讨免疫系统在LDR抑制肿瘤中的作用，并验证了免疫系统在1Gy高剂量辐射(HDR)对免疫功能的损害中的关键作用。此外，在这个小鼠模型中，通过连续的HDR治疗也观察到了LDR诱导的免疫系统的适应性反应。我们发现LDR激活了T细胞和自然杀伤细胞，并增加了脾细胞的细胞毒作用和T细胞在肿瘤组织中的渗透。相反，当HDR预处理的免疫功能受损时，LDR不能诱导肿瘤抑制。而LDR先于HDR给药，可保护机体免疫免受损害，并在一定程度上抑制肿瘤生长，提示LDR可诱导免疫适应性反应。因此，我们证明了免疫增强在LDR诱导的肿瘤抑制中起着关键作用。这些发现强调了免疫反应在肿瘤放射治疗中的重要性，并有助于促进LDR作为一种新的临床应用方法的应用。
Although low‐dose radiation (LDR) possesses the two distinct functions of inducing hormesis and adaptive responses, which result in immune enhancement and tumor inhibition, its clinical applications have not yet been elucidated. The major obstacle that hinders the application of LDR in the clinical setting is that the mechanisms underlying induction of tumor inhibition are unclear, and the risks associated with LDR are still unknown. Thus, to overcome this obstacle and elucidate the mechanisms mediating the antitumor effects of LDR, in this study, we established an in vivo lung cancer model to investigate the participation of the immune system in LDR‐induced tumor inhibition and validated the pivotal role of the immune system by impairing immunity with high‐dose radiation (HDR) of 1 Gy. Additionally, the LDR‐induced adaptive response of the immune system was also observed by sequential HDR treatment in this mouse model. We found that LDR‐activated T cells and natural killer cells and increased the cytotoxicity of splenocytes and the infiltration of T cells in the tumor tissues. In contrast, when immune function was impaired by HDR pretreatment, LDR could not induce tumor inhibition. However, when LDR was administered before HDR, the immunity could be protected from impairment, and tumor growth could be inhibited to some extent, indicating the induction of the immune adaptive response by LDR. Therefore, we demonstrated that immune enhancement played a key role in LDR‐induced tumor inhibition. These findings emphasized the importance of the immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.
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影响因子：
2
作者：
Liang, Xinyue;So, You Ho;Li, Wei
通讯作者：
Li, Wei
影响因子：
3.4
作者：
Jiang, Hongyu;Xu, Ying;Wang, Guanjun
通讯作者：
Wang, Guanjun
影响因子：
12.4
作者：
Lall, R.;Ganapathy, S.;Yuan, Z-M
通讯作者：
Yuan, Z-M
影响因子：
3.4
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
通讯作者：
Finkelstein, JN
DOI：
10.1016/j.ijrobp.2013.08.044
发表时间：
2013-12-01
影响因子：
7
作者：
Kane, Jonathan;Krueger, Sarah A.;Madlambayan, Gerard J.
通讯作者：
Madlambayan, Gerard J.