RNA-Seq-Based TCR Profiling Reveals Persistently Increased Intratumoral Clonality in Responders to Anti-PD-1 Therapy
RNA-Seq-Based TCR Profiling Reveals Persistently Increased Intratumoral Clonality in Responders to Anti-PD-1 Therapy
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基于 RNA 测序的 TCR 分析揭示抗 PD-1 治疗应答者瘤内克隆性持续增加
DOI：
10.3389/fonc.2020.00385
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发表时间：
2020
影响因子：
4.7
通讯作者：
G. Sharonov
中科院分区：
文献类型：
--
作者：
E. Zhigalova;A. Izosimova;D. Yuzhakova;L. N. Volchkova;I. Shagina;M. A. Turchaninova;E. Serebrovskaya;E. Zagaynova;D. Chudakov;G. Sharonov
大量的努力正在投入到寻找外周或肿瘤内T细胞受体（TCR）库的功能，可以预测免疫治疗的反应。在这里，我们展示了MiXCR软件在从分选的肿瘤浸润T和B细胞获得的RNA-Seq数据中提取TCR和免疫球蛋白库方面的实用性。我们使用这种方法从抗PD-1治疗后的HKP 1（KrasG 12 Dp 53 −/−）同基因肺癌小鼠模型中分选的肿瘤浸润性CD 4+和CD 8 + T细胞获得的RNA-Seq数据中提取TCR库。对于这两个亚群，我们证明了TCR多样性对治疗的反应降低。在稍后的时间点，库多样性在进展性疾病中恢复，但在CD 4+和CD 8+亚群中对治疗的应答者中仍然降低。这些观察结果补充了先前的研究，并表明抗PD-1/PD-L1治疗后稳定增加的肿瘤内CD 4+和CD 8 + T细胞克隆性可作为长期缓解的预测因子。
Substantial effort is being invested in the search for peripheral or intratumoral T cell receptor (TCR) repertoire features that could predict the response to immunotherapy. Here we demonstrate the utility of MiXCR software for TCR and immunoglobulin repertoire extraction from RNA-Seq data obtained from sorted tumor-infiltrating T and B cells. We use this approach to extract TCR repertoires from RNA-Seq data obtained from sorted tumor-infiltrating CD4+ and CD8+ T cells in an HKP1 (KrasG12Dp53−/−) syngeneic mouse model of lung cancer after anti-PD-1 treatment. For both subsets, we demonstrate decreased TCR diversity in response to therapy. At a later time point, repertoire diversity is restored in progressing disease but remains decreased in responders to therapy in both CD4+ and CD8+ subsets. These observations complement previous studies and suggest that stably increased intratumoral CD4+ and CD8+ T cell clonality after anti-PD-1/PD-L1 therapy could serve as a predictor of long-term response.
影响因子：
8
作者：
Markowitz, Geoffrey J.;Havel, Lauren S.;Mittal, Vivek
通讯作者：
Mittal, Vivek
影响因子：
8
作者：
Hopkins, Alexander C.;Yarchoan, Mark;Jaffee, Elizabeth M.
通讯作者：
Jaffee, Elizabeth M.
影响因子：
8.8
作者：
Choi, Hyejin;Sheng, Jianting;Mittal, Vivek
通讯作者：
Mittal, Vivek