Integrative spatial omics reveals distinct tumor-promoting multicellular niches and immunosuppressive mechanisms in Black American and White American patients with TNBC

Qian Zhu (), Akhila Balasubramanian, Jaya Ruth Asirvatham, Megha Chatterjee, Badrajee Piyarathna, Jaspreet Kaur, Nada Mohamed, Ling Wu, Stacy Wang, Niloufar Pourfarrokh, Paula Danika Binsol, Mahak Bhargava, Uttam Rasaily, Yitian Xu, Junjun Zheng, Deborah Jebakumar, Arundhati Rao, Carolina Gutierrez, Angela R. Omilian, Carl Morrison, Gokul M. Das, Christine Ambrosone, Erin H. Seeley, Shu-hsia Chen, Yi Li, Eric Chang, Xiaoxian Li, Elizabeth Baker, Ritu Aneja, Xiang H.-F. Zhang and Arun Sreekumar ()
Additional contact information
Qian Zhu: Baylor College of Medicine
Akhila Balasubramanian: Baylor College of Medicine
Jaya Ruth Asirvatham: Baylor Scott and White Health
Megha Chatterjee: Baylor College of Medicine
Badrajee Piyarathna: Baylor College of Medicine
Jaspreet Kaur: Georgia State University
Nada Mohamed: Baylor Scott and White Health
Ling Wu: Baylor College of Medicine
Stacy Wang: Baylor College of Medicine
Niloufar Pourfarrokh: Baylor Scott and White Health
Paula Danika Binsol: Baylor Scott and White Health
Mahak Bhargava: The University of Alabama at Birmingham
Uttam Rasaily: Baylor College of Medicine
Yitian Xu: Houston Methodist Research Institute
Junjun Zheng: Houston Methodist Research Institute
Deborah Jebakumar: Baylor Scott and White Health
Arundhati Rao: Baylor Scott and White Health
Carolina Gutierrez: Baylor College of Medicine
Angela R. Omilian: Roswell Park Comprehensive Cancer Center
Carl Morrison: Roswell Park Comprehensive Cancer Center
Gokul M. Das: Roswell Park Comprehensive Cancer Center
Christine Ambrosone: Roswell Park Comprehensive Cancer Center
Erin H. Seeley: The University of Texas at Austin
Shu-hsia Chen: Houston Methodist Research Institute
Yi Li: Baylor College of Medicine
Eric Chang: Baylor College of Medicine
Xiaoxian Li: Emory University
Elizabeth Baker: The University of Alabama at Birmingham
Ritu Aneja: The University of Alabama at Birmingham
Xiang H.-F. Zhang: Baylor College of Medicine
Arun Sreekumar: Baylor College of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61034-3

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