Spatial and genomic profiling of residual breast cancer after neoadjuvant chemotherapy unveil divergent fates for each breast cancer subtype.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-06-17 Epub Date: 2025-06-06 DOI:10.1016/j.xcrm.2025.102164

Eun Seop Seo, Sabin Park, Eun Yoon Cho, Jeong Eon Lee, Hae Hyun Jung, Jiyeon Hyeon, Sepil An, Seok Won Kim, Junghoon Shin, Jin Seok Ahn, Yeon Hee Park, Young-Hyuck Im, Hoon Kim, Semin Lee, Woong-Yang Park, Ji-Yeon Kim

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引用次数: 0

Abstract

Residual cancer burden (RCB) is a strong prognostic marker after neoadjuvant chemotherapy (NAC) in breast cancer (BC), yet some BCs defy their predicted outcomes. Using single-cell spatial transcriptomics and genomic profiling, we investigate mechanisms underlying divergent fates of BCs with high RCB across subtypes. In triple-negative BC (TNBC), CXCL9+ macrophage-CD8⁺ T cell interactions via chemokines and interferon-gamma signaling promote favorable outcomes, while SPP1+ macrophage-cancer cell interactions driven by hypoxia signaling correlate with poor prognosis. In non-TNBC, the extent of basal-like cancer cells and their proximity to scarce immune cells are linked to prognosis. Additionally, tumor-intrinsic features-such as homologous recombination deficiency in hormone receptor (HR)-positive cancers and structural variations, including extrachromosomal ERBB2 DNA in human epidermal growth factor receptor 2 (HER2)-positive cancers-predict worse outcomes. This study highlights distinct genomic and microenvironmental strategies governing BC subtype-specific fates after NAC.

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新辅助化疗后残留乳腺癌的空间和基因组分析揭示了每种乳腺癌亚型的不同命运。

残留肿瘤负担（RCB）是乳腺癌（BC）新辅助化疗（NAC）后预后的一个重要指标，但一些BC无法达到预期结果。利用单细胞空间转录组学和基因组分析，我们研究了高RCB亚型的bc不同命运的机制。在三阴性BC （TNBC）中，CXCL9+巨噬细胞- cd8 + T细胞通过趋化因子和干扰素- γ信号相互作用促进良好的结果，而SPP1+巨噬细胞-癌细胞相互作用由缺氧信号驱动与不良预后相关。在非tnbc中，基底样癌细胞的范围及其与稀缺免疫细胞的接近程度与预后有关。此外，肿瘤固有特征——如激素受体（HR）阳性癌症的同源重组缺陷和结构变异，包括人表皮生长因子受体2 （HER2）阳性癌症的染色体外ERBB2 DNA——预示着更糟糕的结果。这项研究强调了NAC后控制BC亚型特异性命运的不同基因组和微环境策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.