PO.TB10.06 · 肿瘤生物学
使用Cell DIVE成像对同基因小鼠模型中肿瘤微环境进行多重空间分析
Multiplexed spatial profiling of the tumor microenvironment in syngeneic mouse models using Cell DIVE imaging
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
在临床前模型中对肿瘤免疫微环境(TIME)进行全面的空间和表型表征,对于理解免疫调节和耐药机制至关重要。在本研究中,我们采用Cell DIVE™多重免疫荧光平台,使用来自Cell Signaling Technology(CST)的一组靶向上皮、基质、免疫和检查点标志物的抗体,对同基因小鼠肿瘤模型——MC38(结直肠)和LL/2(肺)——的福尔马林固定石蜡包埋(FFPE)切片进行空间分析。使用Aivia软件分析多重成像数据,以实现细胞级分割、表型分类和空间背景分析。我们对两种肿瘤类型的TME进行了全面比较,揭示了不同的免疫和基质细胞组成,包括细胞毒性细胞、调节性T细胞和巨噬细胞亚群的差异性浸润。AI驱动的空间分析揭示了免疫细胞定位和检查点分子表达的独特模式,凸显了免疫排斥和耗竭的潜在机制。共定位和邻近分析进一步阐明了免疫细胞与肿瘤细胞之间的相互作用,为每种模型的免疫原性提供了洞察。本研究展示了多重、空间解析免疫荧光在剖析同基因小鼠模型中复杂肿瘤免疫微环境方面的实用性。该方法能够更深入地理解临床前模型中的肿瘤免疫生物学,并为识别与治疗反应相关的空间生物标志物模式奠定基础。高度验证的单克隆抗体偶联物、Cell DIVE™多重技术与先进的AI驱动图像分析相结合,为免疫肿瘤学(IO)治疗药物的临床前评估创造了一个更强大、更全面的工具。
查看英文原文 English abstract
Comprehensive spatial and phenotypic characterization of the tumor immune microenvironment (TIME) in preclinical models is essential for understanding mechanisms of immune modulation and resistance. In this study, we employed the Cell DIVE™ multiplex immunofluorescence platform to spatially profile formalin-fixed paraffin-embedded (FFPE) sections from syngeneic mouse tumor models-MC38 (colorectal) and LL/2 (lung)-using a panel of antibodies from Cell Signaling Technology (CST), targeting epithelial, stromal, immune, and checkpoint markers. Multiplexed imaging data were analyzed using Aivia software to enable cell-level segmentation, phenotype classification, and spatial context analysis. We conducted a comprehensive comparison of the TME between the two tumor types, revealing distinct immune and stromal cell compositions, including differential infiltration of cytotoxic cells, regulatory T cells, and macrophage subsets. AI-powered spatial analyses uncovered unique patterns of immune cell localization and checkpoint molecule expression, highlighting potential mechanisms of immune exclusion and exhaustion. Co-localization and proximity analyses further elucidated interactions between immune and tumor cells, offering insights into the immunogenicity of each model. This study demonstrates the utility of multiplexed, spatially resolved immunofluorescence to dissect the complex tumor immune microenvironment in syngeneic mouse models. This approach enables a deeper understanding of tumor immunobiology in preclinical models and provides a foundation for identifying spatial biomarker patterns associated with therapeutic response. The combination of highly validated monoclonal antibody conjugates, Cell DIVE™ multiplexing, and advanced AI-powered image analysis, creates a more powerful and comprehensive tool for preclinical evaluation of immune-oncology (IO) therapeutics.
利益披露 Disclosure
J. Fisher, None..
E. Alonzo, None..
V. Agrawal, None..
S. Struble, None..
R. A. Heil-Chapdelaine, None..
N. F. Diaz Granados, None..
A. Bose, None.