Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy
Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy
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DOI：
10.1186/s40425-019-0589-x
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发表时间：
2019-05-06
影响因子：
10.9
通讯作者：
Steele, Keith E.
中科院分区：
文献类型：
--
作者：
Althammer, Sonja;Tan, Tze Heng;Steele, Keith E.
背景资料：靶向程序性细胞死亡-1（PD 1）/程序性细胞死亡配体-1（PD-L1）通路的免疫检查点疗法（ICT）改善了非小细胞肺癌（NSCLC）患者的结局，特别是PD-L1高表达患者。然而，手动PD-L1评分的预测价值并不完美，需要替代措施。我们报告了一种自动图像分析解决方案，以确定基线肿瘤活检组织中PD-L1+细胞和CD 8+肿瘤浸润淋巴细胞（TIL）密度（CD 8xPD-L1签名）的预测和预后价值。方法：通过免疫组织化学分析存档或新鲜肿瘤活检组织中PD-L1和CD 8的表达。从研究1108/NCT 01693562中的163例患者中采集样本，该研究是一项I/II期试验，旨在评估durvalumab在多种肿瘤类型（包括NSCLC）中的作用，另一个队列为199例非ICT患者。使用Developer XD（TM）2.7软件应用的定制算法对数字图像的PD-L1+和CD 8+细胞密度进行自动评分。结果：对于接受durvalumab的患者，CD 8xPD-L1特征阳性患者的中位总生存期（OS）为21.0个月，而特征阴性患者为7.8个月（p = 0.00002）。与高密度的CD 8+细胞、高密度的PD-L1+细胞或手动评估的肿瘤细胞PD-L1表达>= 25%相比，CD 8xPD-L1特征提供了更大的OS分层。CD 8xPD-L1签名没有分层OS在非ICT患者，虽然高密度的CD 8+细胞与较高的中位OS（高：67个月;低：39.5个月，p = 0.0009）在这一组：自动化的CD 8xPD-L1签名可能有助于确定非小细胞肺癌患者与改善响应度伐鲁单抗治疗。我们的数据也支持CD 8 + TILS在未接受ICT的NSCLC患者中的预后价值。
Background: Immune checkpoint therapies (ICTs) targeting the programmed cell death-1 (PD1)/programmed cell death ligand-1 (PD-L1) pathway have improved outcomes for patients with non-small cell lung cancer (NSCLC), particularly those with high PD-L1 expression. However, the predictive value of manual PD-L1 scoring is imperfect and alternative measures are needed. We report an automated image analysis solution to determine the predictive and prognostic values of the product of PD-L1+ cell and CD8+ tumor infiltrating lymphocyte (TIL) densities (CD8xPD-L1 signature) in baseline tumor biopsies.Methods: Archival or fresh tumor biopsies were analyzed for PD-L1 and CD8 expression by immunohistochemistry. Samples were collected from 163 patients in Study 1108/NCT01693562, a Phase 1/2 trial to evaluate durvalumab across multiple tumor types, including NSCLC, and a separate cohort of 199 non-ICT- patients. Digital images were automatically scored for PD-L1+ and CD8+ cell densities using customized algorithms applied with Developer XD (TM) 2.7 software.Results: For patients who received durvalumab, median overall survival (OS) was 21.0 months for CD8xPD-L1 signature-positive patients and 7.8 months for signature-negative patients (p = 0.00002). The CD8xPD-L1 signature provided greater stratification of OS than high densities of CD8+ cells, high densities of PD-L1+ cells, or manually assessed tumor cell PD-L1 expression >= 25%. The CD8xPD-L1 signature did not stratify OS in non-ICT patients, although a high density of CD8+ cells was associated with higher median OS (high: 67 months; low: 39.5 months, p = 0.0009) in this group.Conclusions: An automated CD8xPD-L1 signature may help to identify NSCLC patients with improved response to durvalumab therapy. Our data also support the prognostic value of CD8+ TILS in NSCLC patients who do not receive ICT.