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
- Arun Sreekumar
2025-07-17
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.