瑞士苏黎世大学Bernd Bodenmiller团队提出了基于基底腔肿瘤细胞和肿瘤空间结构的乳腺癌分层系统。这一研究成果于2025年7月17日发表在国际顶尖学术期刊《癌细胞》上。

为了更好地了解复发的驱动因素，该团队使用成像细胞术来表征215名TNBC患者的肿瘤表型。该课题组人员观察到11种肿瘤细胞表型具有高度的肿瘤间异质性，每种肿瘤细胞表型在个体患者中占主导地位，并鉴定出具有降低基底管谱系保真度和茎样性状的肿瘤细胞表型与快速疾病复发相关。肿瘤-CD8⁺ T细胞相互作用评分可识别炎症性肿瘤和高HLADR表达的患者。研究小组将这些特征结合在8个队列中3737名患者的多组学分析中，通过肿瘤细胞角蛋白表达谱和CD8⁺ T细胞空间模式来区分5种预后乳腺癌亚型。这种分层方案具有直接的临床意义：炎症性肿瘤预后良好，免疫治疗应答率高，而基底管肿瘤细胞为主的患者预后较差。

据悉，快速复发在三阴性乳腺癌（TNBC）中很常见。

附：英文原文

Title: A stratification system for breast cancer based on basoluminal tumor cells and spatial tumor architecture

Author: Lasse Meyer, Hartland W. Jackson, Nils Eling, Shan Zhao, Genki Usui, Haithem Dakhli, Peter Schraml, Susanne Dettwiler, Constanze Elfgen, Zsuzsanna Varga, Holger Moch, Natalie de Souza, Bernd Bodenmiller

Issue&Volume: 2025-07-17

Abstract: Rapid recurrence is common in triple-negative breast cancer (TNBC). To better understand drivers of recurrence, we use imaging mass cytometry to characterize the tumor phenotype landscapes of 215 TNBC patients. We observe high intertumor heterogeneity with eleven tumor cell phenotypes, each of which dominates in an individual patient, and identify a tumor cell phenotype with reduced basoluminal lineage fidelity and stem-like traits that is correlated with rapid disease recurrence. Scoring of tumor-CD8+ T cell interactions identifies patients with inflamed tumors and high HLADR expression. We combine these features in multi-omics analyses of 8 cohorts with 3737 patients across all molecular subtypes to propose five prognostic breast cancer subtypes distinguished by tumor cytokeratin expression profiles and CD8+ T cell spatial patterns. This stratification scheme has direct clinical implications: inflamed tumors show good prognosis and high immunotherapy response rates, whereas patients dominated by basoluminal tumor cells have poor prognosis.

DOI: 10.1016/j.ccell.2025.06.019

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00269-7