Single-cell sequencing revealed the necessity of macrophages in brain microenvironment remodeling by breast cancer metastasis

Maotang Liu; CenZhu Wang; Qin Hu; XueChao Wu; Qing Wang; Jing Wang; Kun Xu; XiaoJie Lu; Wei Tian

doi:10.1016/j.tranon.2025.102287

Single-cell sequencing revealed the necessity of macrophages in brain microenvironment remodeling by breast cancer metastasis

Transl Oncol. 2025 Jan 20:53:102287. doi: 10.1016/j.tranon.2025.102287. Online ahead of print.

Authors

Maotang Liu¹, CenZhu Wang², Qin Hu³, XueChao Wu⁴, Qing Wang⁴, Jing Wang⁴, Kun Xu⁵, XiaoJie Lu⁶, Wei Tian⁷

Affiliations

¹ Department of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, 300041, China; Department of Neurosurgery, The Affiliated Wuxi No.2 People's Hospital, Wuxi 214002, China; Wuxi Neurosurgical Institute, Wuxi, Jiangsu Province, 214002, China.
² Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China.
³ Department of Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing 210009, China.
⁴ Department of Neurosurgery, The Affiliated Wuxi No.2 People's Hospital, Wuxi 214002, China; Wuxi Neurosurgical Institute, Wuxi, Jiangsu Province, 214002, China.
⁵ Department of Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing 210009, China. Electronic address: [email protected].
⁶ Department of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, 300041, China; Department of Neurosurgery, The Affiliated Wuxi No.2 People's Hospital, Wuxi 214002, China; Wuxi Neurosurgical Institute, Wuxi, Jiangsu Province, 214002, China; Nanjing Medical University, Nanjing, Jiangsu Province, 211166, China. Electronic address: [email protected].
⁷ Department of Neurosurgery, The Affiliated Wuxi No.2 People's Hospital, Wuxi 214002, China; Wuxi Neurosurgical Institute, Wuxi, Jiangsu Province, 214002, China; Nanjing Medical University, Nanjing, Jiangsu Province, 211166, China. Electronic address: [email protected].

PMID: 39837060
DOI: 10.1016/j.tranon.2025.102287

Abstract

Breast cancer is one of the most common cancers worldwide, 30-50 % of patients with advanced breast cancer develop brain metastasis, causing severe damage to their life quality. Due to the existence of the blood-brain barrier (BBB), brain lesions were recognized to be a unique microenvironment with limited infiltration of circulating immune cells and drugs. However, emerging studies reported the immunology of the brain tumor microenvironment (TME) and indicated the potential of immunotherapy against brain metastases. Therefore, it is of great value to comprehensively investigate the TME and identify the pro-tumoral mechanisms facilitating brain metastases and the crucial molecules involved in this process. In this research, we re-analyzed public data on three brain surgical specimens of breast cancer metastases and identified the immunosuppressive roles of macrophages in the metastatic TME. Then, we conducted the first single-cell RNA sequencing on a murine model of breast cancer brain metastasis. In the brain TME, immune cells showed prominent heterogeneity, especially the mononuclear phagocyte system (MPS). We identified the alteration of macrophage subclusters in the central nerve system (CNS) after breast cancer invasion and found that metastatic cancer cells re-shaped the TME cellular interactions for immune evasion and nutrition supply. Finally, this research could serve as a reference for further analysis of new therapies against brain metastatic lesions.

Keywords: Brain metastasis; Breast cancer; Single cell RNA-seq; Tumor microenvironment.