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Updated: Nov 14, 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
Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis
Carlota Rubio-Perez1, Ester Planas-Rigol1, Juan L Trincado2,3
1Vall d Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, 08035, Barcelona, Spain.
Abstract:
Brain metastases are the most common tumor of the brain with a dismal prognosis. A fraction of patients with brain metastasis benefit from treatment with immune checkpoint inhibitors (ICI) and the degree and phenotype of the immune cell infiltration has been used to predict response to ICI. However, the anatomical location of brain lesions limits access to tumor material to characterize the immune phenotype. Here, we characterize immune cells present in brain lesions and matched cerebrospinal fluid (CSF) using single-cell RNA sequencing combined with T cell receptor genotyping. Tumor immune infiltration and specifically CD8+ T cell infiltration can be discerned through the analysis of the CSF. Consistently, identical T cell receptor clonotypes are detected in brain lesions and CSF, confirming cell exchange between these compartments. The analysis of immune cells of the CSF can provide a non-invasive alternative to predict the response to ICI, as well as identify the T cell receptor clonotypes present in brain metastasis.
Insights
Analyzing cerebrospinal fluid (CSF) immune cells offers a non-invasive method to predict response to immune checkpoint inhibitors (ICI) in brain metastases. This approach identifies T cell receptor clonotypes, mirroring those in brain lesions.
Area of Science:
- Neuro-oncology
- Immunology
- Genomics
Background:
- Brain metastases are the most frequent brain tumors, associated with poor patient outcomes.
- Immune checkpoint inhibitors (ICI) benefit a subset of patients, with immune cell infiltration predicting response.
- Obtaining tumor tissue from brain lesions for immune profiling is challenging due to anatomical location.
Purpose of the Study:
- To characterize immune cells within brain lesions and matched cerebrospinal fluid (CSF).
- To evaluate CSF immune cell analysis as a non-invasive method for predicting ICI response in brain metastases.
- To identify T cell receptor (TCR) clonotypes in brain metastases via CSF analysis.
Main Methods:
- Single-cell RNA sequencing of immune cells from brain lesions and CSF.
- T cell receptor (TCR) genotyping of immune cells.
- Comparative analysis of immune cell populations and TCR clonotypes between CSF and brain lesions.
Main Results:
- CSF analysis effectively discerns tumor immune infiltration, particularly CD8+ T cells, in brain metastases.
- Identical TCR clonotypes were detected in both brain lesions and CSF, confirming cellular exchange.
- CSF immune cell profiles correlate with tumor-infiltrating lymphocytes, suggesting predictive potential.
Conclusions:
- Cerebrospinal fluid (CSF) immune cell profiling provides a non-invasive alternative for assessing brain metastasis immune microenvironment.
- CSF analysis can predict response to immune checkpoint inhibitors (ICI) by characterizing T cell infiltration.
- This method allows for the identification of T cell receptor clonotypes present in brain metastases.
