Our understanding of how checkpoint inhibitors (CPI) 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 and identified a dynamic awakening of the immune system revealed by T cell evolution in response to treatment. We sequenced T cell receptors (TCR) in plasma cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMC) and performed phenotypic analysis of peripheral T cell subsets from metastatic melanoma patients treated with CPI. We found that early peripheral T cell turnover and TCR 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 using minimally invasive liquid biopsies."

中文翻译：

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一个周期的免疫治疗后，外周 T 细胞动力学揭示了免疫觉醒。

我们对检查点抑制剂 (CPI) 如何影响 T 细胞进化的理解并不完整，这限制了我们从这些药物中获得全面临床获益的能力。在这里，我们分析了一个 CPI 周期后的外周 T 细胞群，并确定了 T 细胞进化响应治疗所揭示的免疫系统的动态唤醒。我们对血浆游离 DNA (cfDNA) 和外周血单核细胞 (PBMC) 中的 T 细胞受体 (TCR) 进行了测序，并对接受 CPI 治疗的转移性黑色素瘤患者的外周 T 细胞亚群进行了表型分析。我们发现早期外周 T 细胞更新和 TCR 库动态可确定哪些患者会对治疗产生反应。此外，我们称之为 TIE 细胞的免疫效应外周 T 细胞子集的扩增与反应相关。这些事件具有预后意义，并且发生在开始免疫治疗后 3 周内，从而提高了使用微创液体活检监测患者反应的潜力。”