Ecotypes of triple-negative breast cancer in response to chemotherapy
9 affiliations
- 1Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX, USA
- 2Graduate School of Biomedical Sciences, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA
- 3Department of Genetics, UT MD Anderson Cancer Center, Houston, TX, USA
- 4Department of Breast Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA
- 5Abdominal Imaging Department, UT MD Anderson Cancer Center, Houston, TX, USA
- 6Department of Pathology, UT MD Anderson Cancer Center, Houston, TX, USA
- 7Department of Surgery, Baylor Medical College, Houston, TX, USA
- 8Department of Breast Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA. [email protected]
- 9Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX, USA. [email protected]
Abstract
. 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.
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BibTeX
@article{yan2026ecotypes,
title = {{Ecotypes of triple-negative breast cancer in response to chemotherapy}},
author = {Yun Yan and Yiyun Lin and Tapsi Kumar and Shanshan Bai and Aatish Thennavan and Jianzhuo Li and Emi Sei and Tuan M. Tran and Min Hu and Mitchell Rao and Chenling Tang and Siyuan He and Tod D. Casasent and Elizabeth E. Ravenberg and Gaiane Margishvili Rauch and Alyson R. Clayborn and Debu Tripathy and Alastair M. Thompson and Bora Lim and Lei Huo and SL Moulder and Clinton Yam and Nicholas E. Navin},
journal = {Nature},
year = {2026},
month = may,
doi = {10.1038/s41586-026-10469-9},
url = {https://doi.org/10.1038/s41586-026-10469-9},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ecotypes of triple-negative breast cancer in response to chemotherapy
AU - Yun Yan
AU - Yiyun Lin
AU - Tapsi Kumar
AU - Shanshan Bai
AU - Aatish Thennavan
AU - Jianzhuo Li
AU - Emi Sei
AU - Tuan M. Tran
AU - Min Hu
AU - Mitchell Rao
AU - Chenling Tang
AU - Siyuan He
AU - Tod D. Casasent
AU - Elizabeth E. Ravenberg
AU - Gaiane Margishvili Rauch
AU - Alyson R. Clayborn
AU - Debu Tripathy
AU - Alastair M. Thompson
AU - Bora Lim
AU - Lei Huo
AU - SL Moulder
AU - Clinton Yam
AU - Nicholas E. Navin
PY - 2026
DA - 2026/05/13
JO - Nature
DO - 10.1038/s41586-026-10469-9
UR - https://doi.org/10.1038/s41586-026-10469-9
AB - . 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.
SN - 0028-0836
SN - 1476-4687
ER -