PO.CL01.05 · 临床研究
CXCL10/11和CCL19双重显色检测法可补充非小细胞肺癌中的PD-L1免疫组织化学
A CXCL10/11 and CCL19 duplex chromogenic assay complements PD-L1 immunohistochemistry in non-small cell lung cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
目的:PD-1阻断是晚期非小细胞肺癌(NSCLC)的标准一线治疗。通过免疫组织化学(IHC)检测的PD-L1肿瘤比例评分(TPS)是预测PD-1阻断反应的关键指标,但并不完善,这凸显了对额外预测性生物标志物的需求。免疫枢纽(immunity hubs)和干性免疫枢纽(stem-immunity hubs)已被证明与反应相关,但这些主要通过空间转录组学和多重免疫荧光进行表征,而这些方法难以在临床工作流程中轻易扩展。我们开发了一种临床兼容的显色双重检测法,利用趋化因子CXCL10/11和CCL19量化这些多细胞免疫网络以预测反应。
实验设计:我们使用显色原位杂交(cISH)对65例转移性NSCLC肿瘤组织进行CXCL10/11和CCL19染色。我们创建了三种独立的评分方法:1. CXCL10/11+细胞的百分比;2. CXCL10/11+瓦片(免疫枢纽)的百分比;3. CXCL10/11+和CCL19+瓦片(干性免疫枢纽)的百分比,以便对患者进行分层并确定各评分方法是否可预测反应。使用RECIST v1.1评估客观缓解率。
结果:识别出57例接受单药PD-(L)1抑制剂治疗的NSCLC患者,并在治疗前采集样本。大多数患者(56%)的PD-L1 TPS为50%或以上。在整个队列中,总缓解率为37%,中位无进展生存期为119天。PD-L1 TPS(>50%)的灵敏度为71.4%,特异度为56.3%,阳性预测值为50%,阴性预测值为75%(Fisher精确检验:p=0.089)。cISH的干性免疫枢纽评分方法与PD-L1 TPS联合使用时,灵敏度为100%,特异度为53%,阳性预测值为58%,阴性预测值为100%(Fisher精确检验:p<0.0001)。值得注意的是,干性免疫cISH评分方法识别出了所有此前未被归类为PD-L1 TPS高的反应者。
结论:利用CXCL10/11和CCL19通过cISH检测干性免疫枢纽可补充PD-L1 IHC。将这一空间生物标志物与PD-L1检测相结合可能有助于优化NSCLC的免疫治疗策略。
查看英文原文 English abstract
Purpose: PD-1 blockade is a standard first-line treatment for advanced non-small cell lung cancer (NSCLC). PD-L1 tumor proportion score (TPS) by immunohistochemistry (IHC), a key predictor of response to PD-1 blockade, is imperfect, underscoring the need for additional predictive biomarkers. Immunity hubs and stem-immunity hubs have been shown to correlate with response, but these have been mainly characterized through spatial transcriptomics, and multiplexed immunofluorescence, which are not readily scalable to clinical workflows. We developed a clinically compatible chromogenic duplex assay that quantifies these multicellular immune networks using the chemokines CXCL10/11 and CCL19 to predict response.
Experimental Design: We stained tissue from 65 metastatic NSCLC tumors for CXCL10/11 and CCL19 using chromogenic in situ hybridization (cISH). We created three separate scoring approaches, 1. percentage of CXCL10/11+ cells, 2. percentage of CXCL10/11+ tiles (immunity hubs), and 3. percentage of CXCL10/11+ and CCL19+ tiles (stem-immunity hubs), in order to stratify patients and determine whether respective scoring approaches were predictive of response. Objective response rates were assessed using RECIST v1.1.
Results: 57 patients with NSCLC treated with single-agent PD-(L)1 inhibitors were identified and samples were procured before treatment. The majority of patients (56%) had a PD-L1 TPS of 50% or above. Across the cohort, the overall response rate was 37% and the median progression free survival of 119 days. The PD-L1 TPS (>50%) had 71.4% sensitivity, 56.3% specificity, 50% positive predictive value, and 75% negative predictive value (Fisher's exact test: p=0.089). The stem-immunity hub scoring approach with cISH combined with PD-L1 TPS had 100% sensitivity, 53% specificity, 58% positive predictive value, and 100% negative predictive value (Fisher's exact test: p<0.0001). Notably, the stem-immunity cISH scoring approach identified all responders who were not previously classified as PD-L1 TPS high.
Conclusions: cISH detection of stem-immunity hubs using CXCL10/11 and CCL19 complements PD-L1 IHC. Integration of this spatial biomarker with PD-L1 testing may refine immunotherapy treatment strategies in NSCLC.
利益披露 Disclosure
A. L. Tang, None..
L. Elmelech, None..
W. L. Tang, None..
M. Spurrell, None..
M. Ganci, None..
Y. He, None..
C. B. Meador, None..
C. S. Nabel, None..
J. J. Lin, None..
M. Mino-Kenudson, None..
N. Hacohen, None..
J. F. Gainor, None..
J. H. Chen, None.