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Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-21789-x

2041-1723

Carlota Rubio-Pérez, Ester Planas‐Rigol, Juan L. Trincado, Ester Bonfill‐Teixidor, Alexandra Arias, Doménica Marchese, Cátia Moutinho, Garazi Serna, Leire Pedrosa, Raffaella Iurlaro, Francisco Martínez‐Ricarte, Laura Escudero, Esteban Cordero, Marta Cicuéndez, Sara Ruiz, Genı́s Parra, Paolo Nucíforo, José Juan González Sánchez, Estela Pineda, Juan Sahuquillo, Josep Tabernero, Holger Heyn, Joan Seoane,

Cancer Immunotherapy and Biomarkers

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.