整合空间组学揭示了美国黑人与白人三阴性乳腺癌患者中不同的促肿瘤多细胞生态位和免疫抑制机制。

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

作者信息

Zhu Qian, Balasubramanian Akhila, Asirvatham Jaya Ruth, Chatterjee Megha, Piyarathna Badrajee, Kaur Jaspreet, Mohamed Nada, Wu Ling, Wang Stacy, Pourfarrokh Niloufar, Binsol Paula Danika, Bhargava Mahak, Rasaily Uttam, Xu Yitian, Zheng Junjun, Jebakumar Deborah, Rao Arundhati, Gutierrez Carolina, Omilian Angela R, Morrison Carl, Das Gokul M, Ambrosone Christine, Seeley Erin H, Chen Shu-Hsia, Li Yi, Chang Eric, Li Xiaoxian, Baker Elizabeth, Aneja Ritu, Zhang Xiang H-F, Sreekumar Arun

机构信息

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.

出版信息

Nat Commun. 2025 Jul 17;16(1):6584. doi: 10.1038/s41467-025-61034-3.

DOI:10.1038/s41467-025-61034-3

PMID:40675986

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.

摘要

三阴性乳腺癌（TNBC）临床结局中的种族差异已有充分记录，但潜在的生物学机制仍知之甚少。为了研究这些差异，我们采用了一种多组学方法，将成像质谱流式细胞术和空间转录组学相结合，以表征自我认定的美国黑人（BA）和美国白人（WA）TNBC患者的肿瘤微环境（TME）。我们的分析表明，BA患者的TME以内皮细胞、巨噬细胞和间充质样细胞网络为特征，这与患者生存率降低相关。相比之下，WA TNBC微环境富含T细胞和中性粒细胞，表明T细胞耗竭和免疫反应受到抑制。配体-受体和通路分析进一步表明，BA TNBC肿瘤表现出相对“免疫冷”的特征，而WA TNBC肿瘤表现出“炎症性”TME的特征，提示一种独特的免疫抑制机制的演变。这些发现为种族上不同的肿瘤促进和免疫抑制微环境提供了见解，这可能是BA和WA TNBC患者临床结局存在差异的原因。