Deep sequencing of the T cell receptor visualizes reconstitution of T cell immunity in mogamulizumab-treated adult T cell leukemia. Oncoimmunology
Deep sequencing of the T cell receptor visualizes reconstitution of T cell immunity in mogamulizumab-treated adult T cell leukemia. Oncoimmunology
复制标题
T 细胞受体的深度测序可显示 mogamulizumab 治疗的成人 T 细胞白血病中 T 细胞免疫的重建。
DOI：
10.1080/2162402x.2017.1405204
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发表时间：
2017
期刊：
影响因子：
7.2
通讯作者：
Kimura S
中科院分区：
文献类型：
--
作者：
3.Shindo T;Kitaura K;Ureshino H;Kamachi K;Miyahara M;Doi K;Watanabe T;Sueoka E;Shin-I T;Suzuki R;Kimura S
尽管抗CCR4抗体mogamulizumab（莫加）对成人T细胞白血病（ATL）显示出惊人的抗肿瘤活性，但它也可能导致致命的免疫病理学，如严重皮疹和移植物抗宿主病，这可能归因于CCR4+调节性T细胞的耗竭。我们以前表明，下一代测序能够精确分析T细胞受体（TCR）库，我们在这里使用该技术来揭示moga治疗的ATL患者的免疫动力学。用莫加处理导致克隆细胞的显著减少或消除，并增强非肿瘤多克隆CD4+T细胞和寡克隆CD8+T细胞的重建。有趣的是，浸润moga相关皮疹的皮肤T细胞在外周血中不共享相同的主要克隆，这使交叉反应的可能性最小化。因此，TCR的深度测序可以揭示moga处理的ATL的免疫重建，并提供对其作用模式的有力见解。
Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4+regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients. Treatment with moga resulted in remarkable reduction or elimination of clonal cells, and enhanced reconstitution of non-tumor polyclonal CD4+T cells and oligoclonal CD8+T cells. Interestingly, cutaneous T cells infiltrating moga-related skin rashes did not share the same major clones in peripheral blood, which minimizes the possibility of cross-reaction. Thus, deep sequencing of the TCR can reveal the immune reconstitution of moga-treated ATL and provides powerful insights into its mode of action.