Characterization of the immune microenvironment in brain metastases from different solid tumors
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Updated: Dec 29, 2025
Quantifying the Brain Metastatic Tumor Micro-Environment using an Organ-On-A Chip 3D Model, Machine Learning, and Confocal Tomography
Published on: August 16, 2020
Jinling Jiang1, Lihong Wu2, Fei Yuan3
1Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Background:
Brain metastases are one of the most common intracranial neoplasms. Increasing evidence have indicated that systemic immunotherapy may provide long-term benefits for brain metastases. Herein, we presented the results of an immune oncology panel RNA sequencing platform for patients with brain metastases from different primary sites.
Methods:
We investigated 25 samples of human brain metastases from lung cancer (n = 12), breast cancer (n = 6), and colorectal cancer (n = 7). Besides, 13 paired samples of adjacent noncancerous brain tissue (10 from patients with lung cancer and 3 from patients with breast cancer) were collected as controls. By comparing the brain metastases and paired samples of adjacent noncancerous brain tissue from 13 patients, we detected three upregulated and six downregulated genes, representing the malignant properties of cancer cells and increased immune infiltration in the microenvironment. Next, we profiled the immune-related genes in brain metastases from three primary cancer types.
Results:
A group of genes were significantly overexpressed in the microenvironment of brain metastases from lung cancer, covering the checkpoint pathways, lymphocyte infiltration, and TCR-coexpression. Especially, immune checkpoint molecules, PD-L1, PD-L2, and IDO1 were expressed at higher levels in brain metastases from lung cancer than those from the other two cancer types.
Conclusions:
This study presents an immune landscape of brain metastases from different cancer types. With high RNA expression levels of PD-1/PD-L1 axis and immune infiltration in brain metastases, it would be worthwhile to explore the efficacy of immune checkpoint blockade for lung cancer patients with intracranial metastases.
Insights
This study analyzed brain metastases from lung, breast, and colorectal cancers. Lung cancer brain metastases showed higher expression of immune checkpoint molecules like PD-L1, suggesting potential immunotherapy benefits.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Brain metastases are common intracranial neoplasms.
- Systemic immunotherapy shows promise for brain metastases.
- Understanding the immune microenvironment is crucial for treatment.
Purpose of the Study:
- To profile the immune landscape of brain metastases from different primary cancer types using RNA sequencing.
- To identify differentially expressed genes and immune-related pathways in brain metastases.
- To compare immune profiles between lung, breast, and colorectal cancer brain metastases.
Main Methods:
- RNA sequencing of 25 human brain metastases (lung, breast, colorectal cancer) and 13 paired noncancerous brain tissues.
- Differential gene expression analysis to identify upregulated and downregulated genes.
- Profiling of immune-related genes, including checkpoint pathways and lymphocyte infiltration.
Main Results:
- Three genes were upregulated and six downregulated in brain metastases compared to normal brain tissue.
- Lung cancer brain metastases exhibited significant overexpression of immune-related genes.
- Higher expression of immune checkpoint molecules (PD-L1, PD-L2, IDO1) was observed in lung cancer brain metastases.
Conclusions:
- The study provides an immune landscape of brain metastases across different cancer types.
- High expression of the PD-1/PD-L1 axis and immune infiltration in lung cancer brain metastases warrants further investigation.
- Immune checkpoint blockade may be a promising therapeutic strategy for lung cancer patients with intracranial metastases.
