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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月17日

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  • 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

摘要

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.