德克萨斯大学Nicholas Navin小组取得一项新突破。他们研究出化疗对三阴性乳腺癌生态型的影响。2026年5月13日出版的《自然》发表了这项成果。

本研究利用了接受新辅助化疗的未接受治疗的TNBC患者的预处理组织样本，并对101例患者的427,857个细胞进行了单细胞转录组分析，对44例患者进行了空间转录组分析。该研究团队将TNBC肿瘤分为4个患者水平亚型（原型），主题是癌细胞基因表达，并确定了13个反映单细胞水平肿瘤内异质性的元程序。TNBC肿瘤微环境由49种免疫和基质细胞状态组成，其中许多状态相对于正常乳腺组织被重新编程。

此外，基于癌细胞和肿瘤微环境细胞类型的共同出现及其在组织中的空间组织，课题组确定了8种不同的细胞群落（生态型）。与之前对T细胞的研究相反，他们的数据显示巨噬细胞亚型和癌细胞元程序对干扰素信号传导、人类白细胞抗原表达和细胞周期活性的重要性，这些都与新辅助化疗的良好反应有关。总的来说，这项研究为未经治疗的TNBC肿瘤的生物学及其与化疗反应的关系提供了新的见解。

据悉，三阴性乳腺癌（TNBC）是一种侵袭性亚型，经常使用化疗治疗，但只有一半的患者反应良好并具有良好的临床结果。

附：英文原文

Title: Ecotypes of triple-negative breast cancer in response to chemotherapy

Author: Yan, Yun, Lin, Yiyun, Kumar, Tapsi, Bai, Shanshan, Thennavan, Aatish, Li, Jianzhuo, Sei, Emi, Tran, Tuan, Hu, Min, Rao, Mitchell, Tang, Chenling, He, Siyuan, Casasent, Anna, Ravenberg, Elizabeth, Rauch, Gaiane Margishvili, Clayborn, Alyson R., Tripathy, Debu, Thompson, Alastair, Lim, Bora, Huo, Lei, Moulder, Stacy, Yam, Clinton, Navin, Nicholas

Issue&Volume: 2026-05-13

Abstract: Triple-negative breast cancer (TNBC) is an aggressive subtype that is frequently treated with chemotherapy, but only half of the patients respond well and have good clinical outcome1,2. Here we leveraged pretreatment tissue samples from treatment-naive patients with TNBC who received neoadjuvant chemotherapy and performed single-cell transcriptomic analysis of 427,857 cells from 101 patients and spatial transcriptomic analysis of 44 patients. We classified TNBC tumours into 4 patient-level subtypes (archetypes) using the cancer-cell gene expression and identified 13 metaprograms that reflect intra-tumoural heterogeneity at the single-cell level. The TNBC tumour microenvironment consisted of 49 immune and stromal cell states, many of which were reprogrammed relative to normal breast tissues. Furthermore, we identified eight distinct cellular communities (ecotypes) on the basis of the co-occurrences of cancer cells and tumour microenvironment cell types, and their spatial organization in tissues. In contrast to previous studies on T cells, our data show the importance of macrophage subtypes and cancer-cell metaprograms for interferon signalling, human leukocyte antigen expression and cell cycle activity that are associated with a good response to neoadjuvant chemotherapy. Collectively, this study provides new insights into the biology of untreated TNBC tumours and their association with chemotherapy response.

DOI: 10.1038/s41586-026-10469-9

Source: https://www.nature.com/articles/s41586-026-10469-9