文章目录

免疫治疗一个周期后外周T细胞动力学揭示的免疫觉醒

原文发布日期：2020-02-10

英文摘要：

摘要翻译：

原文链接：

文章：

免疫治疗一个周期后外周T细胞动力学揭示的免疫觉醒

Immune awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy

原文发布日期：2020-02-10

英文摘要：

Our understanding of how checkpoint inhibitors (CPIs) affect T cell evolution is incomplete, limiting our ability to achieve full clinical benefit from these drugs. Here, we analyzed peripheral T cell populations after one cycle of CPI treatment and identified a dynamic awakening of the immune system, as revealed by T cell evolution in response to treatment. We sequenced T cell receptors in plasma cell-free DNA and peripheral blood mononuclear cells and performed phenotypic analysis of peripheral T cell subsets from patients with metastatic melanoma treated with CPIs. We found that early peripheral T cell turnover and T cell receptor repertoire dynamics identified which patients would respond to treatment. Additionally, the expansion of a subset of immune effector peripheral T cells we call TIE cells correlated with response. These events are prognostic and occur within 3 weeks of starting immunotherapy, raising the potential for monitoring patients’ responses by using minimally invasive liquid biopsies.

摘要翻译：

我们对检查点抑制剂（CPIs）如何影响 T 细胞发育的理解尚不完善，限制了我们从这些药物中获得完全临床益处的能力。在这里，我们分析了接受过一轮 CPI 治疗的外围 T 细胞群，并发现了免疫系统在治疗后出现的动态觉醒现象。通过测序 plasma 中的细胞核 DNA 和外周血单核细胞中的 T 细胞受体，我们对接受治疗的转移性黑色素瘤患者的外周 T 细胞亚群体进行了表型分析。我们发现，早期的外围 T 细胞更新和 T 细胞受体库动力学决定了哪些患者会 respond to treatment。此外，被我们称为 TIE 的免疫效应器细胞群的扩展与响应相关。这些事件具有预测性，并在开始免疫治疗后 3 周内发生，这为使用非侵入性液体活检监测患者的应答提供了潜力。