PO.CL01.22 · 临床研究

基于Delta样配体3(DLL3)的富集可实现小细胞肺癌免疫治疗期间循环肿瘤细胞的灵敏特异检测

Delta-like ligand 3 (DLL3)-based enrichment enables sensitive and specific detection of circulating tumor cells during immunotherapy in small-cell lung cancer

编号 1071 展板 11 时间 4/19 02:00–05:00 区域 Section 42 主讲 Hyung-Joo Oh, MD

分会场 Circulating Tumor Cells, Metastasis, and Dissemination Biology 1

该海报暂无可下载的资料 AACR 官方页面

作者与单位 Authors & Affiliations

Hyung-Joo Oh¹, Hyun-Ju Cho¹, Seung-Hee Song¹, Yoo-Duk Choi², Woo-Jae Son³, Jin-Han Bae³, In-Jae Oh¹, Young-Chul Kim¹, Hae Ung Lee³, Cheol-Kyu Park¹

¹Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Jeollanam-do, Korea, Republic of,²Pathology, Chonnam National University Medical School, Gwangju, Korea, Republic of,³CTCELLS, Inc., Seoul, Korea, Republic of

摘要 Abstract

中文摘要

背景：Delta样配体3(DLL3)是一种Notch受体配体，在小细胞肺癌(SCLC)中高表达，已成为一个有前景的治疗靶点。循环肿瘤细胞(CTCs)在SCLC中含量丰富，与外周血中多种免疫细胞群相互作用。本研究探讨DLL3作为生物标志物增强CTC检测及监测SCLC免疫治疗反应的潜力。方法：我们纳入了17例广泛期(ES)SCLC患者及5例IV期非小细胞肺癌(NSCLC；作为对照)患者，所有患者均计划接受免疫检查点抑制剂或双特异性T细胞衔接器治疗。在治疗前及治疗期间采集全血(6 mL)。CTCs使用CTCeptor™(一种全自动、基于负性清除的连续离心微流控系统)富集，并分为三种表型：pan-cytokeratin(CK)+/DLL3-/CD45-、CK-/DLL3+/CD45-或CK+/DLL3+/CD45-。通过免疫组化对基线肿瘤样本进行SCLC分子亚型及DLL3分析。结果：在接受atezolizumab联合化疗或tarlatamab治疗前，所有ES-SCLC患者(100%)均检测到DLL3+/CD45- CTCs，中位计数为23(范围7-121)，中位大小为9.71 μm(7.33-12.18)。相比之下，NSCLC患者中未检测到DLL3+/CD45- CTCs，仅观察到CK+/DLL3-/CD45- CTCs(1-4个细胞)。在ES-SCLC患者中，CK-/DLL3+/CD45-细胞为主要亚型(63.3%，522/825)，而CK+/DLL3+/CD45- CTCs占所有检测到CTCs的27.7%(228/825)，代表了单独基于CK检测未能捕获的额外CTCs。ASCL1是最常见的分子亚型(12/17)，DLL3的H评分最高(中位数185；范围20-300)。值得注意的是，DLL3+ CTC的数量或比例与DLL3 H评分之间未观察到相关性(r=-0.163，p=0.578)，而DLL3+ CTCs在NEUROD1及POU2F3亚型中仍普遍存在。此外，在atezolizumab化疗2个周期内或tarlatamab治疗1周后，总CTC计数及DLL3+ CTC计数均显著下降。结论：利用CTCeptor™可高效、特异地在ES-SCLC患者中检测DLL3+ CTCs，作为CK之外用于CTC鉴定的补充标志物。DLL3在CTCs中出现的频率高于肿瘤组织。这些发现支持DLL3作为ES-SCLC中基于CTC监测的潜在生物标志物，并有必要在包括免疫学特征分析在内的更大队列中进一步验证。

查看英文原文 English abstract

Background: Delta-like Ligand 3 (DLL3), a Notch receptor ligand, is highly expressed in small cell lung cancer (SCLC) and has emerged as a promising therapeutic target. Circulating tumor cells (CTCs), abundant in SCLC, interact with diverse immune cell populations in peripheral blood. This study investigates the potential of DLL3 as a biomarker to enhance CTC detection and monitor immunotherapy response in SCLC. Methods: We enrolled 17 patients with extensive-stage (ES) SCLC and 5 with stage IV non-small cell lung cancer (NSCLC; as controls), all scheduled for an immune checkpoint inhibitor or a bispecific T-cell engager. Whole blood (6 mL) was collected before and during treatment. CTCs were enriched using CTCeptor TM , a fully automated, negative depletion-based continuous centrifugal microfluidic system, and classified into three phenotypes: pan-cytokeratin (CK) + /DLL3 - /CD45 - , CK - /DLL3 + /CD45 - , or CK + /DLL3 + /CD45 - . Baseline tumor samples were analyzed by immunohistochemistry for SCLC molecular subtypes and DLL3. Results: DLL3 + /CD45 - CTCs were detected in all ES-SCLC patients (100%) prior to treatment with atezolizumab plus chemotherapy or tarlatamab, with a median count of 23 (range 7-121) and a median size of 9.71 μm (7.33-12.18). In contrast, no DLL3 + /CD45 - CTCs were detected in NSCLC patients, where only CK + /DLL3 - /CD45 - CTCs were observed (1-4 cells). Among ES-SCLC patients, CK - /DLL3 + /CD45 - cells were the predominant subtype (63.3%, 522/825), while CK + /DLL3 + /CD45 - CTCs accounted for 27.7% (228/825) of all detected CTCs, representing additional CTCs not captured by CK-based detection alone. ASCL1 was the most prevalent molecular subtype (12/17), with DLL3 exhibiting the highest H-score (median, 185; range, 20-300). Notably, no correlation was observed between the number or proportion of DLL3 + CTC and the DLL3 H-score ( r = -0.163, p = 0.578), while DLL3 + CTCs remained prevalent in NERUDO1 and POU2F3 subtypes. Furthermore, both total and DLL3 + CTC counts markedly decreased within 2 cycles of atezolizumab chemotherapy or 1 week after tarlatamab treatment. Conclusion: DLL3 + CTCs can be efficiently and specifically detected in ES-SCLC patients using CTCeptor TM , serving as a complementary marker to CK for CTC identification. DLL3 appears more frequently in CTCs than in tumor tissue. These findings support DLL3 as a potential biomarker for CTC-based monitoring in ES-SCLC and warrant further validation in larger cohorts, including analyses of immunologic features.

利益披露 Disclosure

H. Oh, None.. H. Cho, None.. S. Song, None.. Y. Choi, None. W. Son, CTCELLS, Inc. Employment. J. Bae, CTCELLS, Inc. Employment. I. Oh, None.. Y. Kim, None. H. Lee, CTCELLS, Inc. Employment. C. Park, None.

← 返回 AACR 2026 检索