Characterization of the cryoablation-induced immune response in kidney cancer patients
Characterization of the cryoablation-induced immune response in kidney cancer patients
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DOI：
10.1080/2162402x.2017.1326441
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Nakamura, Yusuke
中科院分区：
文献类型：
--
作者：
Kato, Taigo;Iwasaki, Tomoyuki;Nakamura, Yusuke
冷冻消融术是肾癌的治疗方式之一，预计会诱导强烈的局部免疫反应以及全身T细胞介导的免疫反应，可能导致远处转移病灶消退。因此，治疗前后肿瘤中T细胞库和免疫环境的表征应有助于更好地理解冷冻消融诱导的抗癌免疫应答。在这项研究中，我们收集了22名肾癌患者的肿瘤组织，在冷冻消融术前和冷冻消融术后3个月。此外，在相同的时间点从14名患者中采集血液样本。我们应用新一代测序方法，使用从肿瘤组织和外周血单核细胞分离的RNA来表征T细胞受体β（TCRB）库。TCRB库分析揭示了通过冷冻消融在肿瘤组织中某些T细胞克隆的扩增。我们还发现，与冷冻消融前肿瘤样品相比，冷冻消融后组织样品中丰富的TCRB克隆型（定义为在总TCRB读数中具有>= 1%频率的克隆型）的比例显著增加。发现这些TCRB克隆型中的一些在外周血中增加。免疫相关基因在冷冻消融前后组织中的表达分析显示，在冷冻消融后组织样品中，CD 8（+）、CD 4（+）、颗粒酶A（GZMA）和CD 11 c的转录水平显著升高沿着并且CD 8/FOXP 3比率较高。我们的研究结果表明，冷冻消融术可以诱导肿瘤中强烈的免疫反应，抗肿瘤T细胞的寡克隆扩增，这些T细胞在全身循环。
Cryoablation is one of treatment modalities for kidney cancer and is expected to induce strong local immune responses as well as systemic T-cell-mediated immune reactions that may lead to the regression of distant metastatic lesions. Thus, the characterization of T cell repertoire and immune environment in tumors before and after treatment should contribute to the better understanding of the cryoablation-induced anticancer immune responses. In this study, we collected tumor tissues from 22 kidney cancer patients, before cryoablation and at 3 mo after cryoablation. In addition, blood samples were collected from 14 patients at the same time points. We applied a next generation sequencing approach to characterize T cell receptor beta (TCRB) repertoires using RNAs isolated from tumor tissues and peripheral blood mononuclear cells. TCRB repertoire analysis revealed the expansion of certain T cell clones in tumor tissues by cryoablation. We also found that proportions of abundant TCRB clonotypes (defined as clonotypes with >= 1% frequency among total TCRB reads) were significantly increased in the post-cryoablation tissue samples than those of pre-cryoablation tumor samples. Some of these TCRB clonotypes were found to be increased in peripheral blood. Expression analysis of immune-related genes in the tissues of pre- and post-cryoablation showed significantly elevated transcriptional levels of CD8(+), CD4(+), Granzyme A (GZMA), and CD11c along with a high CD8/FOXP3 ratio in the post-cryoablation tissue samples. Our findings revealed that cryoablation could induce strong immune reactions in tumors with oligoclonal expansion of antitumor T cells, which circulate systemically.