The multiomic tumor microenvironment landscape of invasive lobular carcinoma of the breast.

• DOI: 10.1200/jco.2024.42.16_suppl.1044
• Publication Date: 2024-05-29T16:58:26Z
• Authors: Jason A Mouabbi; Funda Meric-Bernstam; Azadeh Nasrazadani; Blessie Elizabeth...; Basim Salem; Vladimir Kushnarev; Arina Tkachuk; Maria Sotova; Margarita Polyakova; Oleg Baranov; Polina Turova; Konstantin Cherny...; Nikita Kotlov; Jessica H. Brown; Patrick Clayton; Alexander Sarachakov; Ekaterina Postova...; Alexander Bagaev; Debashish Tripathy; Rachel M. Layman
• Keywords: Invasive lobular carcinoma

1044 Background: The tumor microenvironment (TME) in invasive lobular carcinoma (ILC) has been shown to play a critical role progression and therapeutic response. However, dissecting the complexity heterogeneity of TME requires advanced profiling techniques that overcome limitations traditional histopathological methods. This study leverages single-cell spatial phenotyping using multiplex immunofluorescence (MxIF) integrated with RNA sequencing (RNA-seq) evaluate landscape ILC. Methods: MxIF was performed by processing 2,139,084 cells from FFPE whole-slide tissues treatment naïve, de novo metastatic ILC patients treated at MD Anderson Cancer Center PhenoCycler system. Prepared slides were stained comprehensive panel 27 biomarkers delineate immune cells, checkpoints, tissue structure, predictive (i.e., ER, PR, HER2). Bulk RNA-seq performed, employing Kassandra cell deconvolution algorithm (1) for profiling, enabling multi-omic correlation Spearman’s rank coefficient phenotypes transcriptomic data (single expression gene signatures). Signature enrichment scores calculated ssGSEA (2). Transcriptome-based subtyping functional signatures as described ref (3). Results: Using MxIF, 14 primary populations 25 distinct stromal subtypes delineated within TME. analysis enabled us categorize into three major groups analysis: Immune Enriched Non-Fibrotic (IE; 37% samples), Highly Vascularized (HV; 30% Immune-Enriched Fibrotic (IE-F; 23% samples). Each type demonstrated unique revealed corresponding derived subtypes. IE group displayed robust presence minimal fibrosis. Conversely, IE-F there significant fibrosis alongside dense infiltrates evidenced large fraction fibroblasts CD45+ per mm2. CD31+ endothelial predominant HV group, indicating an extensive vascular network. Conclusions: By integrating we present detailed multiomic uncovers intricate Further evaluation this approach can lead development personalized strategies, emphasizing value understanding treating 1. Zyatsev et al., Cell, 2022. 2. Barbie al, Nature, 2009. 3.