单细胞测序揭示伴脑转移乳腺癌患者的免疫景观。

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

机构信息

Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.

Key Laboratory of Molecular Radiation Oncology Hunan Province, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Thorac Cancer. 2024 Mar;15(9):702-714. doi: 10.1111/1759-7714.15243. Epub 2024 Feb 5.

DOI:10.1111/1759-7714.15243

PMID:38316626

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10961220/

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.

摘要

背景

乳腺癌是全球发病率最高的癌症，脑转移（BrM）是最恶性的病例之一。虽然一些患者从免疫检查点抑制剂（ICI）中受益，但由于大脑的复杂解剖结构和转移性肿瘤的异质性，使得对转移性肿瘤的肿瘤免疫微环境（TME）进行特征描述变得困难。

方法

为了解决这个问题，我们使用单细胞 RNA 测序（scRNA-seq）分析了乳腺癌 BrM 患者脑脊液中的免疫细胞，从而全面描绘了 BrM 的免疫微环境景观。

结果

基于典型标记基因，我们鉴定了 9 种细胞类型，并通过差异表达基因（DEG）分析进一步鉴定了它们的亚型。我们比较了不同预后患者的免疫微环境中细胞和功能的变化。我们的分析揭示了一系列促进肿瘤免疫功能的基因（CCR5、LYZ、IGKC、MS4A1 等）和抑制肿瘤免疫功能的基因（SCGB2A2、CD24 等）。