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Characterization of T cell tumor infiltration in brain metastases through the analysis of the cerebrospinal fluid

ABSTRACT: Brain metastases are the most common tumor of the brain with a dismal prognosis. A fraction of patients with brain metastasis benefit from the treatment with immune checkpoint inhibitors (ICI) and tumor inflammation has been used as a biomarker to predict response. However, the anatomical location of brain lesions limits the access to tumor material to determine inflammation rates. We have characterized immune cells present in brain lesions and matched cerebrospinal fluids (CSF), applying single-cell RNA sequencing combined with T cell receptor genotyping. We observed tumor inflammation and CD8Ã¢Â€Â‹ + Ã¢Â€Â‹ T cell infiltration to be recapitulated in the CSF. Consistently, identical T cell receptor clonotypes were detected in brain lesions and CSF, confirming the cell exchange of both compartments. We propose the analysis of immune cells of the CSF to present a non-invasive profiling alternative of brain metastases inflammation states for ICI response prediction and clonotype detection for cell therapy.

PROVIDER: EGAS00001004751 | EGA |

REPOSITORIES: EGA

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