Identification of a novel inflammatory mast cell subpopulation in triple-negative breast cancer
- 1Department of Oncology, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University , ,
- 2Department of Urology and Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University , ,
- 3Department of Medical Imaging, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University , , ,
Abstract
Background: Triple-negative breast cancer (TNBC) is associated with poor therapeutic outcomes, and increasing attention has been directed toward the tumor microenvironment (TME). Mast cells are an important component of the TME, yet their heterogeneity and functional roles in TNBC remain incompletely understood.
Methods: Single-cell RNA sequencing data of TNBC were analyzed using the Seurat pipeline. Mast cells were extracted and re-clustered, and the subpopulations were characterized by functional enrichment, transcription factor, pseudotime, drug sensitivity, and cell–cell communication analyses. The role of the inflammatory subpopulation was further examined using an in silico virtual knockout approach and validated in a 4T1 subcutaneous tumor model in BALB/c mice.
Results: Four transcriptionally distinct mast cell subpopulations were identified. Among them, the C4 subpopulation exhibited a pronounced inflammatory signature and was highly enriched in the NF-κB pathway. C4 was predicted to have lower sensitivity to several first-line chemotherapeutic agents and was associated with an unfavorable treatment response. Cell–cell communication analysis suggested that C4 may suppress CD8 ⁺ T cells through multiple immune-inhibitory signals. In vivo , IL-33 administration increased the proportion of C4 and promoted tumor growth, and the proportion of C4 was positively correlated with tumor volume and weight.
Conclusions: We identified an inflammation-associated mast cell subpopulation (C4) that may contribute to TNBC progression, providing a potential target for future therapeutic exploration.
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BibTeX
@article{li2026identification,
title = {{Identification of a novel inflammatory mast cell subpopulation in triple-negative breast cancer}},
author = {Zehan Li and Ziqing Wu and Lingxin Zeng and Chuzhong Wei and Huazhen Wu and Huisi Qiu and Jianping Chen and Pingmei Zhang and Yuxiao Tian and Fanghui Bian and Jiemin Liang and Dongqian Li and Muyan Liu and Zhiying Li and Yuyi Liu and Meiyi Li and Xiangfeng Cen and Lihuan Zhou and Huodi Chen and Huijuan Jiang and Haosheng Li and Xin Wang and Ruiming Tang and Song Zhu},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1975768},
url = {https://europepmc.org/article/PMC/PMC13668803},
note = {CC BY},
}
RIS
TY - JOUR
TI - Identification of a novel inflammatory mast cell subpopulation in triple-negative breast cancer
AU - Zehan Li
AU - Ziqing Wu
AU - Lingxin Zeng
AU - Chuzhong Wei
AU - Huazhen Wu
AU - Huisi Qiu
AU - Jianping Chen
AU - Pingmei Zhang
AU - Yuxiao Tian
AU - Fanghui Bian
AU - Jiemin Liang
AU - Dongqian Li
AU - Muyan Liu
AU - Zhiying Li
AU - Yuyi Liu
AU - Meiyi Li
AU - Xiangfeng Cen
AU - Lihuan Zhou
AU - Huodi Chen
AU - Huijuan Jiang
AU - Haosheng Li
AU - Xin Wang
AU - Ruiming Tang
AU - Song Zhu
PY - 2026
DA - 2026/10/01
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1975768
UR - https://europepmc.org/article/PMC/PMC13668803
AB - Background: Triple-negative breast cancer (TNBC) is associated with poor therapeutic outcomes, and increasing attention has been directed toward the tumor microenvironment (TME). Mast cells are an important component of the TME, yet their heterogeneity and functional roles in TNBC remain incompletely understood. Methods: Single-cell RNA sequencing data of TNBC were analyzed using the Seurat pipeline. Mast cells were extracted and re-clustered, and the subpopulations were characterized by functional enrichment, transcription factor, pseudotime, drug sensitivity, and cell–cell communication analyses. The role of the inflammatory subpopulation was further examined using an in silico virtual knockout approach and validated in a 4T1 subcutaneous tumor model in BALB/c mice. Results: Four transcriptionally distinct mast cell subpopulations were identified. Among them, the C4 subpopulation exhibited a pronounced inflammatory signature and was highly enriched in the NF-κB pathway. C4 was predicted to have lower sensitivity to several first-line chemotherapeutic agents and was associated with an unfavorable treatment response. Cell–cell communication analysis suggested that C4 may suppress CD8 ⁺ T cells through multiple immune-inhibitory signals. In vivo , IL-33 administration increased the proportion of C4 and promoted tumor growth, and the proportion of C4 was positively correlated with tumor volume and weight. Conclusions: We identified an inflammation-associated mast cell subpopulation (C4) that may contribute to TNBC progression, providing a potential target for future therapeutic exploration.
SN - 1664-3224
ER -