Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21789-x
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Funding
- Fundacion Asociacion Espanola contra el Cancer (AECC)
- FERO (EDM)
- Ramon Areces Foundation
- Cellex Foundation
- BBVA (CAIMI)
- ISCIII, FIS [PI16/01278]
- Ministerio de Ciencia, Innovacion y Universidades (AEI/FEDER, UE) [SAF2017-89109-P]
- Juan de la Cierva formacion fellowship
- Sara Borrell fellowship
- Spanish Ministry of Science and Innovation
- Centro de Excelencia Severo Ochoa
- CERCA Program/Generalitat de Catalunya
- Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III
- Generalitat de Catalunya through Departament de Salut
- Spanish Ministry of Ministry of Science and Innovation
- European Regional Development Fund
- Generalitat de Catalunya through Departament d'Empresa i Coneixement
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Single-cell RNA analysis of cerebrospinal fluid and brain can identify immune cell infiltration and T cell receptor clonotypes in brain metastasis, providing a non-invasive alternative for predicting response to immune checkpoint inhibitors.
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. The use of CSF for diagnosis of metastatic brain tumors could be of clinical and patient benefit. Here the authors undertake a single-cell RNA analysis of CSF and brain to determine whether the phenotype in the CSF is reflective of the phenotype in the tumor.
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