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新技术实现免疫检查点抑制对治疗益处的非侵入性早期识别
作者:小柯机器人 发布时间:2020/10/4 23:00:26

美国斯坦福大学Maximilian Diehn等研究人员实现免疫检查点抑制对治疗益处的非侵入性早期识别。2020年10月1日,《细胞》杂志在线发表了这项成果。

研究人员证明预处理循环肿瘤DNA(ctDNA)和外周CD8 T细胞水平与持久的临床益处(DCB)独立相关。研究人员进一步表明,单次输注后的ctDNA动态可以帮助识别将要实现DCB的患者。通过整合这些决定因素,研究人员开发并验证了一种完全无创的多参数测定(DIREct-On,通过免疫谱分析和ctDNA-On-therapy进行的持久性免疫疗法反应估计),可强有力地预测哪些患者将以比任何单个特征更高的准确性实现DCB。
 
因此,这些结果表明,整合的ctDNA和循环免疫细胞谱分析可以为接受免疫检查点抑制剂(ICI)的非小细胞肺癌(NSCLC)患者提供准确、非侵入性的早期最终结果预测。
 
据介绍,尽管用ICI治疗NSCLC可以产生显著的持久反应,但大多数患者仍会产生早期疾病。此外,通过常规成像进行的初始反应评估通常无法确定哪些患者将获得DCB。
 
附:英文原文

Title: Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition

Author: Barzin Y. Nabet, Mohammad S. Esfahani, Everett J. Moding, Emily G. Hamilton, Jacob J. Chabon, Hira Rizvi, Chloe B. Steen, Aadel A. Chaudhuri, Chih Long Liu, Angela B. Hui, Diego Almanza, Henning Stehr, Linda Gojenola, Rene F. Bonilla, Michael C. Jin, Young-Jun Jeon, Diane Tseng, Cailian Liu, Taha Merghoub, Joel W. Neal, Heather A. Wakelee, Sukhmani K. Padda, Kavitha J. Ramchandran, Millie Das, Andrew J. Plodkowski, Christopher Yoo, Emily L. Chen, Ryan B. Ko, Aaron M. Newman, Matthew D. Hellmann, Ash A. Alizadeh, Maximilian Diehn

Issue&Volume: 2020-10-1

Abstract: Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors(ICIs) can produce remarkably durable responses, most patients develop early diseaseprogression. Furthermore, initial response assessment by conventional imaging is oftenunable to identify which patients will achieve durable clinical benefit (DCB). Here,we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8T cell levels are independently associated with DCB. We further show that ctDNA dynamicsafter a single infusion can aid in identification of patients who will achieve DCB.Integrating these determinants, we developed and validated an entirely noninvasivemultiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immuneprofiling and ctDNA-On-treatment) that robustly predicts which patients will achieveDCB with higher accuracy than any individual feature. Taken together, these resultsdemonstrate that integrated ctDNA and circulating immune cell profiling can provideaccurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patientsreceiving ICIs.

DOI: 10.1016/j.cell.2020.09.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31142-9

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/