Abstract
Abstract It is increasingly clear that triple negative breast cancer (TNBC) is a heterogeneous disease with variable clinical presentation, histological features and response to therapy. While these differences have been partially explained by inter- and intra-tumoral heterogeneity, spatial heterogeneity represented by the tumor architecture plays a critical role in clonal evolution and displays a landscape for different compartment-specific processes and cell-to-cell specific interactions. To better understand the impact of spatial heterogeneity on gene-expression-defined cell populations, we have coupled single-cell RNA sequencing with multiplex immunofluorescence (IF). Multiplex immunofluorescence using specific markers for each cell cluster, integrated with computational image analyses and neighborhood maps, has revealed spatial zonation of single cell subpopulations. Zonation of single cell populations was coupled to hypoxia and overlayed distinct metabolic tumor zones and defined areas of differential stress and cell plasticity that give rise to tumor cells with enhanced fitness and aggressivity. Citation Format: M Park, C Martínez Ramirez, Y Yang, A Blanchet-Cohen, H Kuasne, A Fortier, J Ragoussis, P Savage, A Omeroglou, S Meterissian, S Costantino, C Kleinman. Spatial variance signatures/Intra-tumor zonation in TNBC [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP112.
Published Version
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