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T cell receptor repertoires of ex vivo-expanded tumor-infiltrating lymphocytes from breast cancer patients.
Immunologic Research ( IF 3.3 ) Pub Date : 2020-08-28 , DOI: 10.1007/s12026-020-09150-8
In Ah Park 1 , Hajar Rajaei 2 , Young-Ae Kim 2, 3 , Hyeonjin Lee 2, 3 , Heejae Lee 2, 3 , Jeong-Han Seo 2, 3 , Sun-Hee Heo 2, 3 , In Hye Song 4 , Gyungyub Gong 2 , Hee Jin Lee 2
Affiliation  

A higher level of tumor-infiltrating lymphocytes (TILs) is associated with better prognosis in breast cancer patients. Adoptive transfer of lymphocytes coupled with conventional therapies has appealed to many clinicians and investigators as an effective treatment strategy for cancer patients, which necessitates efficient activation and expansion of cytotoxic T lymphocytes precisely targeting cancer cells. To comprehensively understand composition of TILs and to provide a grounding in adoptive T cell therapy, we analyzed the T cell receptor (TCR) repertoires in ex vivo–expanded TILs from nine breast cancer patients via next-generation sequencing. For the three of them, TCR repertoires of TILs gathered after the initial culture during 2 weeks were additionally analyzed and compared to those of TILs that underwent ex vivo rapid expansion procedure (REP). Diversity of TCR repertoire was variable among the patients. V/J segment usage in the clonotypes was similar among patients, with variable distribution of read counts for each V/J segment. The top 50% of most frequently observed VJ combinations was present in > 80% of the total clonotypes. Compared with TCGA data, the samples contained a similar amount of recurrent CDR3 sequences, but clonotype expansion was variable among the samples. In terms of clinicopathologic factor, presence of in vitro reactivity among triple-negative breast cancer cases seemed to be related to lower Shannon’s index, but p value was not statistically significant. In addition, the proportion of CD45RO+ cells out of CD8+ T cells were negatively correlated with Shannon’s diversity index for both TCRα and TCRβ chains (p = 0.010) via Spearman test. In this study, we identified a heterogeneous pattern of expanded T cell clones and stable usage of V/J segments in ex vivo–expanded TILs from breast cancer patients. Further large-scale studies are requisite to elucidate the clinical significance of TCR repertoires.



中文翻译:

来自乳腺癌患者的体外扩增的肿瘤浸润淋巴细胞的 T 细胞受体库。

较高水平的肿瘤浸润淋巴细胞 (TIL) 与乳腺癌患者更好的预后相关。淋巴细胞的过继转移与常规疗法相结合,作为癌症患者的有效治疗策略吸引了许多临床医生和研究人员,这需要有效激活和扩增精确靶向癌细胞的细胞毒性 T 淋巴细胞。为了全面了解 TIL 的组成并为过继性 T 细胞治疗奠定基础,我们通过下一代测序分析了来自 9 名乳腺癌患者的体外扩增 TIL 中的 T 细胞受体 (TCR) 库。对于他们三人来说,额外分析了在 2 周内初始培养后收集的 TIL 的 TCR 库,并与那些经过体外快速扩增程序 (REP) 的 TIL 进行比较。TCR 库的多样性在患者中是可变的。克隆型中 V/J 片段的使用在患者中相似,每个 V/J 片段的读取计数分布不同。最常观察到的 VJ 组合的前 50% 存在于 > 80% 的总克隆型中。与 TCGA 数据相比,样本包含相似数量的重复 CDR3 序列,但样本之间的克隆型扩展是可变的。在临床病理因素方面,三阴性乳腺癌病例体外反应性的存在似乎与香农指数较低有关,但 克隆型中 V/J 片段的使用在患者中相似,每个 V/J 片段的读取计数分布不同。最常观察到的 VJ 组合的前 50% 存在于 > 80% 的总克隆型中。与 TCGA 数据相比,样本包含相似数量的重复 CDR3 序列,但样本之间的克隆型扩展是可变的。在临床病理因素方面,三阴性乳腺癌病例体外反应性的存在似乎与香农指数较低有关,但 克隆型中 V/J 片段的使用在患者中相似,每个 V/J 片段的读取计数分布不同。最常观察到的 VJ 组合的前 50% 存在于 > 80% 的总克隆型中。与 TCGA 数据相比,样本包含相似数量的重复 CDR3 序列,但样本之间的克隆型扩展是可变的。在临床病理因素方面,三阴性乳腺癌病例体外反应性的存在似乎与香农指数较低有关,但 样本包含相似数量的重复 CDR3 序列,但克隆型扩展在样本之间是可变的。在临床病理因素方面,三阴性乳腺癌病例体外反应性的存在似乎与香农指数较低有关,但 样本包含相似数量的重复 CDR3 序列,但克隆型扩展在样本之间是可变的。在临床病理因素方面,三阴性乳腺癌病例体外反应性的存在似乎与香农指数较低有关,但p值无统计学意义。此外, 通过 Spearman 检验,CD45RO +细胞在 CD8 + T 细胞中的比例与 TCRα 和 TCRβ 链的香农多样性指数呈负相关(p = 0.010)。在这项研究中,我们确定了扩增 T 细胞克隆的异质模式,以及在来自乳腺癌患者的体外扩增 TIL 中 V/J 片段的稳定使用。需要进一步的大规模研究来阐明 TCR 库的临床意义。

更新日期:2020-09-05
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