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Publications

Journal Article Epublish 15 citations

PubMed: 40675986 DOI: 10.1038/s41467-025-61034-3

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

Nat Commun 16(1):6584

Authors: 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

Affiliations

  • Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, USA.
  • Department of Human Molecular Genetics, Baylor College of Medicine, Houston, Texas, USA.
  • Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
  • Department of Molecular Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
  • Department of Pathology, Baylor Scott and White Health, Temple, Texas, USA.
  • Department of Biology, Georgia State University, Atlanta, Georgia, USA.
  • Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas, USA.
  • Department of Human Molecular Genetics, Baylor College of Medicine, Houston, Texas, USA.
  • Department of Nutrition Sciences, School of Health Professions, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
  • Immune Monitoring Core, Houston Methodist Research Institute, Houston, Texas, USA.
  • Department of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
  • Department of Chemistry, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, USA.
  • Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
  • Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine and Division of Pulmonary, Allergy, and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
  • Department of Molecular Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.

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.

MeSH

Cells, Neoplasms