Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition.
Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition.
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DOI：
10.1016/j.cell.2020.09.001
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发表时间：
2020-10-15
期刊：
影响因子：
64.5
通讯作者：
Diehn M
中科院分区：
文献类型：
--
作者：
Nabet BY;Esfahani MS;Moding EJ;Hamilton EG;Chabon JJ;Rizvi H;Steen CB;Chaudhuri AA;Liu CL;Hui AB;Almanza D;Stehr H;Gojenola L;Bonilla RF;Jin MC;Jeon YJ;Tseng D;Liu C;Merghoub T;Neal JW;Wakelee HA;Padda SK;Ramchandran KJ;Das M;Plodkowski AJ;Yoo C;Chen EL;Ko RB;Newman AM;Hellmann MD;Alizadeh AA;Diehn M
虽然用免疫检查点抑制剂（ICI）治疗非小细胞肺癌（NSCLC）可以产生显著持久的反应，但大多数患者会出现早期疾病进展。此外，通过常规成像进行的初始缓解评估通常无法确定哪些患者将获得持久的临床获益（DCB）。在这里，我们证明了治疗前循环肿瘤DNA（ctDNA）和外周CD 8 T细胞水平与DCB独立相关。我们进一步表明，单次输注后的ctDNA动力学可以帮助识别将实现DCB的患者。整合这些决定因素，我们开发并验证了一种完全无创的多参数测定（DIRECT-On，通过免疫分析和ctDNA-治疗进行的持久免疫治疗应答估计），该测定可稳健地预测哪些患者将达到DCB，其准确性高于任何个体特征。总之，这些结果表明，整合ctDNA和循环免疫细胞谱分析可以为接受ICI的NSCLC患者提供准确，无创和早期的最终结局预测。整合治疗前ctDNA和外周CD 8 + T细胞特征以及早期治疗中ctDNA动态的多参数非侵入性模型，在预测非小细胞肺癌患者对免疫检查点阻断治疗的持久临床应答方面显示出希望。
Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICI) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA- On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICI. Multiparameter noninvasive models that integrate pre-treatment ctDNA and peripheral CD8+ T cell features, together with early on-treatment ctDNA dynamics, show promise in predicting durable clinical response to immune checkpoint blockade treatment in patients with non-small cell lung cancer.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
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作者：
Chabon JJ;Simmons AD;Lovejoy AF;Esfahani MS;Newman AM;Haringsma HJ;Kurtz DM;Stehr H;Scherer F;Karlovich CA;Harding TC;Durkin KA;Otterson GA;Purcell WT;Camidge DR;Goldman JW;Sequist LV;Piotrowska Z;Wakelee HA;Neal JW;Alizadeh AA;Diehn M
通讯作者：
Diehn M
影响因子：
50.5
作者：
Lim, C.;Tsao, M. S.;Leighl, N. B.
通讯作者：
Leighl, N. B.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
82.9
作者：
Auslander N;Zhang G;Lee JS;Frederick DT;Miao B;Moll T;Tian T;Wei Z;Madan S;Sullivan RJ;Boland G;Flaherty K;Herlyn M;Ruppin E
通讯作者：
Ruppin E