PO.TB10.03 · 肿瘤生物学
使用六十重多重免疫肿瘤学面板研究原发性与复发性浆液性卵巢癌之间肿瘤免疫微环境的空间演变
Spatial evolution of the tumor immune microenvironment between primary and recurrent serous ovarian cancer using a sixty plex multiplex immuno oncology panel
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摘要 Abstract
中文摘要
背景：尽管治疗取得进展，复发性卵巢癌仍表现出高复发率，且由于强烈的免疫抑制性肿瘤免疫微环境（TIME），免疫检查点抑制剂（ICIs）显示出有限的应答（10-15%）。复发过程中免疫逃逸的机制仍未充分了解，凸显了对TIME重塑进行空间表征以优化生物标志物指导的联合免疫治疗的必要性。
方法：使用来自复发性浆液性卵巢癌患者的福尔马林固定石蜡包埋（FFPE）原发性和复发性肿瘤组织，构建配对组织微阵列（TMAs）。使用Akoya IO60免疫肿瘤学面板进行多重免疫荧光染色。使用Qupath工作流程进行定量空间图像分析，以评估与复发相关的免疫细胞组成、表型和肿瘤-免疫结构变化。
结果：共纳入58例患者，其中35例有配对的原发性和复发性肿瘤标本。根据化疗应答分类，41例患者被归为铂敏感，8例为铂耐药。空间图谱分析正在进行中。初步观察提示原发性和复发性肿瘤之间T细胞亚群（CD3、CD4、CD8）、调节性T细胞（FOXP3+）和免疫抑制性髓系群体（CD163+、CD206+）存在异质性变化，同时免疫检查点通路（PD-1、PD-L1、LAG-3、VISTA）和肿瘤表型（PanCK、EpCAM）也发生改变。
结论：本研究旨在表征复发期间TIME的空间演变，并识别促成治疗耐药的免疫逃逸机制。研究结果有望指导精准免疫治疗策略的开发，并改善复发性卵巢癌患者的临床结局。
查看英文原文 English abstract
Background: Despite advances in treatment, recurrent ovarian cancer continues to exhibit high recurrence rates, and immune checkpoint inhibitors (ICIs) demonstrate limited response (10-15%) due to a strongly immunosuppressive tumor immune microenvironment (TIME). The mechanisms of immune escape during recurrence remain insufficiently understood, highlighting the need for spatial characterization of TIME remodeling to optimize biomarker-guided combination immunotherapy.
Methods: Formalin-fixed paraffin-embedded (FFPE) primary and recurrent tumor tissues from patients with recurrent serous ovarian cancer were used to construct matched tissue microarrays (TMAs). Multiplex immunofluorescence staining was performed using the Akoya IO60 immuno-oncology panel. Quantitative spatial image analysis was conducted using the Qupath workflow to assess immune cell composition, phenotypes, and tumor-immune architecture changes associated with recurrence.
Results: A total of 58 patients were included, of whom 35 had matched primary and recurrent tumor specimens available. Based on chemotherapy response classification, 41 patients were categorized as platinum-sensitive and 8 as platinum-resistant. Spatial profiling analysis is ongoing. Preliminary observations suggest heterogeneous shifts in T-cell subsets (CD3, CD4, CD8), regulatory T cells (FOXP3+), and immunosuppressive myeloid populations (CD163+, CD206+), along with altered immune checkpoint pathways (PD-1, PD-L1, LAG-3, VISTA) and tumor phenotypes (PanCK, EpCAM) between primary and recurrent tumors.
Conclusion: This study aims to characterize spatial evolution of TIME during recurrence and identify immune escape mechanisms contributing to treatment resistance. The findings are expected to guide the development of precision immunotherapy strategies and improve clinical outcomes for patients with recurrent ovarian cancer.
利益披露 Disclosure
H. Shin, None..
J. Kim, None..
Y. Kim, None..
Y. Lee, None..
J. Kim, None.