Brain Metastases Cell Partners and Tumor Microenvironment

García-Gómez, Pedro; Priego, Neibla; Álvaro-Espinosa, Laura; Valiente, Manuel

doi:10.1007/978-3-030-23417-1_5

Cited by 1 publication

(1 citation statement)

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“…Brain metastasis is associated with one of the worst clinical outcomes and has few therapeutic options (1). The brain contains two distinctive compartments-parenchyma mainly consisting of cells and leptomeninges filled with cerebrospinal fluid (CSF) (2).…”

Section: Introductionmentioning

confidence: 99%

VLA-4 suppression by senescence signals regulates meningeal immunity and leptomeningeal metastasis

Huang

Lei

et al. 2022

Preprint

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Leptomeningeal metastasis is associated with dismal prognosis and has few treatment options. However, very little is known about the immune response to leptomeningeal metastasis. Here, by establishing an immunocompetent mouse model of breast cancer leptomeningeal metastasis, we found that tumor-specific CD8+ T cells were generated in deep cervical lymph nodes (dCLNs) and played an important role in controlling leptomeningeal metastasis. Mechanistically, T cells in dCLNs displayed a senescence phenotype and their recruitment was impaired in mice bearing cancer cells that preferentially colonized in leptomeningeal space. Upregulation of p53 suppressed the transcription of VLA-4 in senescent dCLN T cells and consequently inhibited their migration to the leptomeningeal compartment. Clinically, CD8+ T cells from cerebrospinal fluid of patients with leptomeningeal metastasis exhibited senescence and VLA-4 downregulation. Collectively, our findings demonstrated that CD8+ T cell immunosenescence drives leptomeningeal metastasis.

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Section: Introductionmentioning

confidence: 99%