Language

English

Publication Date

7-17-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-61034-3

PMID

40675986

PMCID

PMC12271405

PubMedCentral® Posted Date

7-17-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Racial disparities in the clinical outcomes of triple-negative breast cancer (TNBC) have been well-documented, but the underlying biological mechanisms remain poorly understood. To investigate these disparities, we employed a multi-omic approach integrating imaging mass cytometry and spatial transcriptomics to characterize the tumor microenvironment (TME) in self-identified Black American (BA) and White American (WA) TNBC patients. Our analysis revealed that the TME in BA patients is marked by a network of endothelial cells, macrophages, and mesenchymal-like cells, which correlates with reduced patient survival. In contrast, the WA TNBC microenvironment is enriched in T-cells and neutrophils, indicative of T-cell exhaustion and suppressed immune responses. Ligand-receptor and pathway analyses further demonstrated that BA TNBC tumors exhibit a relatively "immune-cold" profile, while WA TNBC tumors display features of an "inflamed" TME, suggesting the evolution of a unique immunosuppressive mechanism. These findings provide insight into racially distinct tumor-promoting and immunosuppressive microenvironments, which may contribute to the observed differences in clinical outcomes among BA and WA TNBC patients.

Keywords

Female, Humans, Black or African American, Macrophages, T-Lymphocytes, Transcriptome, Triple Negative Breast Neoplasms, Tumor Microenvironment, White, Breast cancer, Cancer microenvironment

Published Open-Access

yes

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