Novel Biomarkers of Dynamic Blood PD-L1 Expression for Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer Patients.
Novel Biomarkers of Dynamic Blood PD-L1 Expression for Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer Patients.
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晚期非小细胞肺癌患者免疫检查点抑制剂动态血液 PD-L1 表达的新生物标志物
DOI：
10.3389/fimmu.2021.665133
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发表时间：
2021
影响因子：
7.3
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Yang Q;Chen M;Gu J;Niu K;Zhao X;Zheng L;Xu Z;Yu Y;Li F;Meng L;Chen Z;Zhuo W;Zhang L;Sun J
背景免疫检查点抑制剂（ICI）最近已成为一种备受关注的恶性肿瘤治疗方案。然而，只有一小部分亚群获得了长期临床获益。如何通过合理的生物标志物选择最佳的患者仍然是一个热门话题。方法收集51例晚期恶性肿瘤患者的配对组织标本和血液标本进行相关性分析。检测晚期非小细胞肺癌（NSCLC）患者经ICIs治疗2个月后血液PD-L1（bPD-L1）表达的动态变化，包括PD-L1 mRNA、exosomal PD-L1（exoPD-L1）蛋白和可溶性PD-L1（sPD-L1）。用R软件计算所有三种生物标志物的无进展生存期（PFS）和总生存期（OS）的最佳截止值。结果51例恶性肿瘤组织中PD-L1（tPD-L1）阳性者PD-L1 mRNA表达水平明显高于tPD-L1阴性者。在40例晚期NSCLC患者中，PD-L1 mRNA倍数变化≥ 2.04的患者PFS、OS和最佳客观缓解率（bOR）较好。此外，在21例晚期NSCLC病例的队列中，还发现exoPD-L1的倍数变化≥ 1.86与更好的疗效和OS相关。sPD-L1的动态变化与疗效和OS无关。此外，PD-L1 mRNA和exoPD-L1的组合可以筛选出更好的患者，以获得ICIs治疗的潜在益处。结论bPD-L1与tPD-L1的表达呈正相关。ICIs治疗早期PD-L1 mRNA、exoPD-L1或两者表达增加可作为晚期NSCLC患者疗效和OS的阳性生物标志物。
Background Immune checkpoint inhibitors (ICIs) have become a high-profile regimen for malignancy recently. However, only a small subpopulation obtains long-term clinical benefit. How to select optimal patients by reasonable biomarkers remains a hot topic. Methods Paired tissue samples and blood samples from 51 patients with advanced malignancies were collected for correlation analysis. Dynamic changes in blood PD-L1 (bPD-L1) expression, including PD-L1 mRNA, exosomal PD-L1 (exoPD-L1) protein and soluble PD-L1 (sPD-L1), were detected after 2 months of ICIs treatment in advanced non-small-cell lung cancer (NSCLC) patients. The best cutoff values for progression-free survival (PFS) and overall survival (OS) of all three biomarkers were calculated with R software. Results In 51 cases of various malignancies, those with positive tissue PD-L1 (tPD-L1) had significantly higher PD-L1 mRNA than those with negative tPD-L1. In 40 advanced NSCLC patients, those with a fold change of PD-L1 mRNA ≥ 2.04 had better PFS, OS and best objective response (bOR) rate. In addition, a fold change of exoPD-L1 ≥ 1.86 was also found to be associated with better efficacy and OS in a cohort of 21 advanced NSCLC cases. The dynamic change of sPD-L1 was not associated with efficacy and OS. Furthermore, the combination of PD-L1 mRNA and exoPD-L1 could screen better patients for potential benefit from ICIs treatment. Conclusion There was a positive correlation between bPD-L1 and tPD-L1 expression. Increased expression of PD-L1 mRNA, exoPD-L1, or both in early stage of ICIs treatment could serve as positive biomarkers of efficacy and OS in advanced NSCLC patients.
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影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
16
作者：
Cordonnier, Marine;Nardin, Charlee;Gobbo, Jessica
通讯作者：
Gobbo, Jessica
影响因子：
50.3
作者：
Becker A;Thakur BK;Weiss JM;Kim HS;Peinado H;Lyden D
通讯作者：
Lyden D
影响因子：
28.4
作者：
Mezquita, Laura;Auclin, Edouard;Besse, Benjamin
通讯作者：
Besse, Benjamin
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators