Integrative spatial omics reveals distinct tumor-promoting multicellular niches and immunosuppressive mechanisms in Black American and White American patients with TNBC
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.
Article Details
Authors (31)
Qian Zhu
Akhila Balasubramanian
Jaya Ruth Asirvatham
Megha Chatterjee
Badrajee Piyarathna
Jaspreet Kaur
Nada Mohamed
Ling Wu
State Key Lab of Photocatalysis on Energy and Environment, College of Chemistry
Stacy Wang
Niloufar Pourfarrokh
Paula Danika Binsol
Mahak Bhargava
Uttam Rasaily
Yitian Xu
Junjun Zheng
Deborah Jebakumar
Arundhati Rao
Carolina Gutierrez
Lester and Sue Smith Breast Center, Baylor College of Medicine
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
Lester and Sue Smith Breast Center, Baylor College of Medicine
Arun Sreekumar
Department of Molecular and Cellular Biology, Baylor College of Medicine