Single-Cell Characterization of SPP1-Expressing Macrophages and Their Predicted Interactions With T Cells in the Breast Cancer Bone Metastatic Microenvironment.
6 affiliations
- 1Department of Pharmacy, Zhejiang Provincial People's Hospital Bijie Hospital (The First People's Hospital of Bijie), Bijie, Guizhou, China.
- 2Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
- 3Hangzhou Medical College, Hangzhou, Zhejiang, China.
- 4Department of Orthopedics, Zhejiang Provincial People's Hospital Bijie Hospital (The First People's Hospital of Bijie), Bijie, Guizhou, China.
- 5Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
- 6Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China.
Abstract
Background
Breast cancer is a highly common malignancy in women, with bone as its most frequent site of distant metastasis significantly increasing mortality risk.Methods
This study integrated single-cell RNA sequencing datasets (GSE266330 and GSE243526) to systematically characterize the tumor microenvironment across normal tissue, primary tumor, and bone metastasis in breast cancer.Results
In total, 141 056 high-quality single cells were analyzed from an integrated cohort comprising a bone-metastasis dataset (GSE266330) and a primary/normal breast dataset (GSE243526), identifying 11 major cell types. Within the bone-metastatic cohort, we identified a macrophage subpopulation highly expressing SPP1 (Mac-SPP1) that exhibited an M2-polarized signature and elevated metabolic gene-set enrichment, and that expressed transcription factors such as HOXA9 and MAF. We also identified CD4-S100A9 and CD8-GZMK T-cell subpopulations with high cytotoxicity, high exhaustion, and metabolic reprogramming. Pseudotime analysis positioned CD4-S100A9 cells at one end of the inferred CD4+ T-cell trajectory and CD8-GZMK cells at an intermediate node along the inferred CD8+ T-cell trajectory. Cell-cell communication analysis predicted that Mac-SPP1 interacts with these T-cell subsets through the SPP1-integrin (e.g., SPP1-CD44) and CD74-MIF/COPA signaling axes.Conclusion
This study provides a single-cell characterization of the breast cancer bone-metastatic microenvironment, identifying an SPP1-expressing macrophage subset (Mac-SPP1) and predicting its interactions with CD4-S100A9 and CD8-GZMK T cells. Because the bone-metastatic and primary/normal specimens derive from different datasets, these findings are descriptive and cannot be attributed to metastatic progression alone and require experimental validation and confirmation in cohorts that profile primary and metastatic specimens within a single study.
Related
- Characterization of 3D heterocellular spheroids of pancreatic ductal adenocarcinoma for the study of cell interactions in the tumor immune microenvironment
- Lipocalin-2-expressing red pulp macrophages link ischemic stroke to systemic immune reprogramming in mice and humans
- Spatial single-cell landscape of tumor-associated macrophages and their crosstalk with the tumor microenvironment
- Tumor-associated macrophages in the tumor immune microenvironment of non-small cell lung cancer
- Mechano-metabolic coupling in the tumor microenvironment: from mechanotransduction to protein lactylation and metastatic cascades
BibTeX
@article{xuan2026singlecell,
title = {{Single-Cell Characterization of SPP1-Expressing Macrophages and Their Predicted Interactions With T Cells in the Breast Cancer Bone Metastatic Microenvironment.}},
author = {Zixue Xuan and Zhongxiu Wu and Yuting Zhong and Jinying Jiang and Yuan Zhang and Lei Cheng and Jun Zhang and Kai Wang},
journal = {Cancer reports (Hoboken, N.J.)},
year = {2026},
month = nov,
doi = {10.1002/cnr2.70732},
url = {https://europepmc.org/article/MED/42968173},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-Cell Characterization of SPP1-Expressing Macrophages and Their Predicted Interactions With T Cells in the Breast Cancer Bone Metastatic Microenvironment.
AU - Zixue Xuan
AU - Zhongxiu Wu
AU - Yuting Zhong
AU - Jinying Jiang
AU - Yuan Zhang
AU - Lei Cheng
AU - Jun Zhang
AU - Kai Wang
PY - 2026
DA - 2026/11/01
JO - Cancer reports (Hoboken, N.J.)
DO - 10.1002/cnr2.70732
UR - https://europepmc.org/article/MED/42968173
AB - Background Breast cancer is a highly common malignancy in women, with bone as its most frequent site of distant metastasis significantly increasing mortality risk.Methods This study integrated single-cell RNA sequencing datasets (GSE266330 and GSE243526) to systematically characterize the tumor microenvironment across normal tissue, primary tumor, and bone metastasis in breast cancer.Results In total, 141 056 high-quality single cells were analyzed from an integrated cohort comprising a bone-metastasis dataset (GSE266330) and a primary/normal breast dataset (GSE243526), identifying 11 major cell types. Within the bone-metastatic cohort, we identified a macrophage subpopulation highly expressing SPP1 (Mac-SPP1) that exhibited an M2-polarized signature and elevated metabolic gene-set enrichment, and that expressed transcription factors such as HOXA9 and MAF. We also identified CD4-S100A9 and CD8-GZMK T-cell subpopulations with high cytotoxicity, high exhaustion, and metabolic reprogramming. Pseudotime analysis positioned CD4-S100A9 cells at one end of the inferred CD4+ T-cell trajectory and CD8-GZMK cells at an intermediate node along the inferred CD8+ T-cell trajectory. Cell-cell communication analysis predicted that Mac-SPP1 interacts with these T-cell subsets through the SPP1-integrin (e.g., SPP1-CD44) and CD74-MIF/COPA signaling axes.Conclusion This study provides a single-cell characterization of the breast cancer bone-metastatic microenvironment, identifying an SPP1-expressing macrophage subset (Mac-SPP1) and predicting its interactions with CD4-S100A9 and CD8-GZMK T cells. Because the bone-metastatic and primary/normal specimens derive from different datasets, these findings are descriptive and cannot be attributed to metastatic progression alone and require experimental validation and confirmation in cohorts that profile primary and metastatic specimens within a single study.
SN - 2573-8348
ER -