Single-cell sequencing reveals the immune landscape of breast cancer patients with brain metastasis.

Huaping Zhou, Xiang He, Jia Huang, Yumin Zhong, Leyao Zhang, Xiang Ao, Hailin Zhao, Su Hu, Hongsheng Li, Jianqing Huang, Hongxin Huang, Hongling Liang
Author Information
  1. Huaping Zhou: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China. ORCID
  2. Xiang He: Key Laboratory of Molecular Radiation Oncology Hunan Province, Xiangya Hospital, Central South University, Changsha, China.
  3. Jia Huang: School of Health Management, Guangzhou Medical University, Guangzhou, China.
  4. Yumin Zhong: Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China.
  5. Leyao Zhang: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  6. Xiang Ao: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  7. Hailin Zhao: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  8. Su Hu: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  9. Hongsheng Li: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  10. Jianqing Huang: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  11. Hongxin Huang: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
  12. Hongling Liang: Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.

Abstract

BACKGROUND: Breast cancer has the highest incidence rate of cancer worldwide, and brain metastases (BrM) are among the most malignant cases. While some patients have benefited from immune checkpoint inhibitors (ICIs), the complex anatomical structure of the brain and the heterogeneity of metastatic tumors have made it difficult to characterize the tumor immune microenvironment (TME) of metastatic tumors.
METHODS: To address this, we used single-cell RNA sequencing (scRNA-seq) to analyze immune cells in the cerebrospinal fluid (CSF) of BrM patients with breast cancer, thereby providing a comprehensive view of the immune microenvironment landscape of BrM.
RESULTS: Based on canonical marker genes, we identified nine cell types, and further identified their subtypes through differential expression gene (DEG) analysis. We compared the changes in cells and functions in the immune microenvironment of patients with different prognoses. Our analysis revealed a series of genes that promote tumor immune function (CCR5, LYZ, IGKC, MS4A1, etc.) and inhibit tumor immune function (SCGB2A2, CD24, etc.).
CONCLUSIONS: The scRNA-seq in CSF provides a noninvasive method to describe the TME of breast cancer patients and guide immunotherapy.

Keywords

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Grants

  1. 202102080096, HL Liang, 201904010331, JQ Huang/Guangzhou S&T Project
  2. 2023A03J0430, HL Liang/Guangzhou S&T City and University United Project
  3. 2022A1515012376, JQ Huang/Project Natural Science Foundation of Guangdong Province
  4. 2021KTSCX091, HL Liang, 2020KTSCX105, JQ Huang/Guangdong Provincial Bureau of Education Project
  5. 20191A011097, HL Liang/Guangzhou Health S&T Project
  6. 202005, HS Li/Clinical Key Specialty Project of Guangzhou Medical University

MeSH Term

Humans
Female
Breast Neoplasms
Brain Neoplasms
Brain
Immune Checkpoint Inhibitors
Immunotherapy
Tumor Microenvironment

Chemicals

Immune Checkpoint Inhibitors

Word Cloud

Created with Highcharts 10.0.0immunecancerpatientsbraintumormicroenvironmentbreastBrMsequencingmetastasesmetastatictumorsTMERNAscRNA-seqcellscerebrospinalfluidCSFlandscapegenesidentifiedanalysisfunctionetcBACKGROUND:BreasthighestincidencerateworldwideamongmalignantcasesbenefitedcheckpointinhibitorsICIscomplexanatomicalstructureheterogeneitymadedifficultcharacterizeMETHODS:addressusedsingle-cellanalyzetherebyprovidingcomprehensiveviewRESULTS:BasedcanonicalmarkerninecelltypessubtypesdifferentialexpressiongeneDEGcomparedchangesfunctionsdifferentprognosesrevealedseriespromoteCCR5LYZIGKCMS4A1inhibitSCGB2A2CD24CONCLUSIONS:providesnoninvasivemethoddescribeguideimmunotherapySingle-cellrevealsmetastasissingle‐cell

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