Impact of high-dose rate radiotherapy on B and natural killer (NK) cell polarization in peripheral blood mononuclear cells (PBMCs) via inducing non-small cell lung cancer (NSCLC)-derived exosomes.
Impact of high-dose rate radiotherapy on B and natural killer (NK) cell polarization in peripheral blood mononuclear cells (PBMCs) via inducing non-small cell lung cancer (NSCLC)-derived exosomes.
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高剂量率放疗通过诱导非小细胞肺癌 (NSCLC) 衍生的外泌体对外周血单核细胞 (PBMC) 中 B 细胞和自然杀伤 (NK) 细胞极化的影响
DOI：
10.21037/tcr-21-536
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发表时间：
2021-07
影响因子：
0.9
通讯作者：
Wu YZ
中科院分区：
文献类型：
--
作者：
Lei QQ;Sui JD;Jin F;Luo HL;Shan JJ;Tang L;Wang Y;Wu YZ
背景非小细胞肺癌（NSCLC）是最常见的实体肿瘤。虽然立体定向体放疗在非小细胞肺癌的抗肿瘤免疫应答中起着重要作用，但剂量率对这种应答的可能影响尚未完全阐明。方法体外培养A549细胞，在Varian TrueBeam®线性加速器上，采用无压平滤波（FFF）技术进行剂量和剂量率递增照射，然后与外周血单个核细胞（PBMCs）共培养。从辐照的A549细胞中分离外泌体，然后与pbmc共培养。用流式细胞术分析淋巴细胞团的比例。结果在剂量率为1000 MU/min时，10 Gy治疗组PBMCs中CD3−免疫细胞团的比例显著高于未照射组和其他低剂量（2,6 Gy）治疗组。然而，未观察到对CD3+ T细胞亚群比例的影响。进一步的结果表明，当剂量率为1200 MU/min时，14 Gy治疗组NK细胞和B细胞比例均达到峰值。值得注意的是，当使用较大的剂量率（1,600 ~ 2,400 MU/min）时，这两种细胞比例在较低的10 Gy辐射剂量下达到峰值。我们进一步发现，与单次低剂量照射（2 Gy）相比，单次高剂量照射（10 Gy）可以显著刺激a549相关外泌体分泌，并呈辐射剂量率依赖性。辐射衍生的超高剂量率外泌体有助于pbmc中B和NK细胞亚群的极化。结论优化的放疗方案取决于适当的放疗剂量和剂量率，可使非小细胞肺癌细胞产生外泌体，并最终使免疫细胞在pbmc中重新分布。
Background Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. While it has been established that stereotactic body radiotherapy for NSCLC plays an important role in antitumor immune response, the possible effects of the dose rate on this response has not been fully clarified. Methods In vitro, A549 cells were irradiated on a Varian TrueBeam® Linear Accelerator with dose and dose rate escalation using the flattening filter-free (FFF) technique, which was followed by coculturing with peripheral blood mononuclear cells (PBMCs). The exosomes from irradiated A549 cells were isolated and then cocultured with PBMCs. Flow cytometry was performed to analyze the proportion of lymph cell clusters in PBMCs. Results The proportion of CD3− immune cell clusters in PBMCs was significantly higher in the 10 Gy treatment group than in the nonirradiated group and other lower-dose (2, 6 Gy) treatment groups at the dose rate of 1,000 MU/min. However, no influence was observed on the proportion of CD3+ T cell subsets. Further results showed that both natural killer (NK) and B cell proportions reached peaks in the 14 Gy treatment group when a dose rate of 1,200 MU/min was used. Notably, the peak values of these two cell proportions were reached at a lower radiation dose of 10 Gy when a greater dose rate, ranging from 1,600 to 2,400 MU/min, was used. We further found that a single, high dose of irradiation (10 Gy), as compared with a single, low dose of irradiation (2 Gy), could markedly stimulate the A549-related exosome secretion in a radiation dose rate-dependent manner. The ultrahigh dose rate radiation–derived exosomes contributed to the polarization of B and NK cell subsets in PBMCs. Conclusions The optimized radiation regime, which depends on the appropriate radiation dose and dose rate, results in the production of exosomes derived from NSCLC cells and eventually the redistribution of immune cells in PBMCs.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
3.1
作者：
Laurent, P. A.;Kownacka, A.;Mirjolet, C.
通讯作者：
Mirjolet, C.
影响因子：
20.3
作者：
Lee, Youjin;Auh, Sogyong L.;Fu, Yang-Xin
通讯作者：
Fu, Yang-Xin
影响因子：
51.1
作者：
Formenti, Silvia C.;Demaria, Sandra
通讯作者：
Demaria, Sandra
DOI：
10.1084/jem.20052494
发表时间：
2006-05-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Reits EA;Hodge JW;Herberts CA;Groothuis TA;Chakraborty M;Wansley EK;Camphausen K;Luiten RM;de Ru AH;Neijssen J;Griekspoor A;Mesman E;Verreck FA;Spits H;Schlom J;van Veelen P;Neefjes JJ
通讯作者：
Neefjes JJ