Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition

被引：251

作者：

Nabet, Barzin Y. ^{[1
,2
]}

Esfahani, Mohammad S. ^{[3
]}

Moding, Everett J. ^{[1
,2
]}

Hamilton, Emily G. ^{[1
,4
]}

Chabon, Jacob J. ^{[1
,5
]}

Rizvi, Hira ^{[6
]}

Steen, Chloe B. ^{[2
]}

Chaudhuri, Aadel A. ^{[7
]}

Liu, Chih Long ^{[2
,3
]}

Hui, Angela B. ^{[1
,2
]}

Almanza, Diego ^{[1
,4
]}

Stehr, Henning ^{[8
]}

Gojenola, Linda ^{[8
]}

Bonilla, Rene F. ^{[1
]}

Jin, Michael C. ^{[3
]}

Jeon, Young-Jun ^{[1
,2
,9
]}

Tseng, Diane ^{[3
]}

Liu, Cailian ^{[10
]}

Merghoub, Taha ^{[10
,11
,12
,13
]}

Neal, Joel W. ^{[2
,3
]}

Wakelee, Heather A. ^{[2
,3
]}

Padda, Sukhmani K. ^{[2
,3
]}

Ramchandran, Kavitha J. ^{[2
,3
]}

Das, Millie ^{[2
,3
,14
]}

Plodkowski, Andrew J. ^{[15
]}

Yoo, Christopher ^{[1
]}

Chen, Emily L. ^{[1
]}

Ko, Ryan B. ^{[1
]}

Newman, Aaron M. ^{[2
,5
,16
]}

Hellmann, Matthew D. ^{[6
,11
,12
,13
]}

Alizadeh, Ash A. ^{[2
,3
,5
]}

Diehn, Maximilian ^{[1
,2
,5
]}

机构：

[1] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA

[2] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Med, Stanford Canc Inst, Div Oncol, Stanford, CA 94305 USA

[4] Stanford Univ, Program Canc Biol, Stanford, CA 94305 USA

[5] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[6] Mem Sloan Kettering Canc Ctr, Druckenmiller Ctr Lung Canc Res, 1275 York Ave, New York, NY 10021 USA

[7] Washington Univ, Sch Med, Dept Genet, Dept Radiat Oncol, St Louis, MO USA

[8] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA

[9] Sungkyunkwan Univ, Dept Integrat Biotechnol, Suwon, South Korea

[10] Mem Sloan Kettering Canc Ctr, Ludwig Collaborat & Swim Amer Lab, 1275 York Ave, New York, NY 10021 USA

[11] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[12] Weill Cornell Sch Med, New York, NY 10065 USA

[13] Mem Sloan Kettering Canc Ctr, Parker Inst Canc Immunotherapy MSK, 1275 York Ave, New York, NY 10021 USA

[14] VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA

[15] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA

[16] Stanford Univ, Dept Biomed Data Sci, Stanford, CA USA

来源：

CELL | 2020年 / 183卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CELL LUNG-CANCER; BLOCKADE; TUMOR; IMMUNOTHERAPY; FRAMEWORK; DYNAMICS; TIME;

D O I：

10.1016/j.cell.2020.09.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) 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 ICIs.

引用

页码：363 / +

页数：27

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