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Reactive astrocytes as a therapeutic target in brain metastasis

19th national competition for scientific and technical research

Precision Medicine and Cancer

Senior Researcher : Manuel Valiente Cortés

Research Centre or Institution : Centro Nacional de Investigaciones Oncológicas (CNIO). Madrid

Abstract

One of the more extreme cases of the inefficacy of available treatments to challenge metastases might be represented by the spread of cancer cells from the original primary tumour to the brain. Highly prevalent cancers (lung cancer, breast cancer and melanoma) are the main source of brain metastasis, affecting 10-30% of patients with advanced cancer. Astrocytes are a brain cell type with an important role in the maintenance of homeostasis during physiology but that change dramatically, both morphologically and functionally, when the central nervous system gets injured. Evidences of phenotypic changes in these reactive astrocytes associated with metastatic cells come from their initial ability to limit the progression of many cancer cells that recently cross the blood-brain barrier, thus behaving as an effective anti-metastatic barrier, while later on, reactive astrocytes have shown to potentiate the growth of surviving cancer cells. Our data generated during this project demonstrate with unprecedented detail the characterization of brain metastasis-associated astrocytes as a major modulator of local immunity as well as the rewired identity of this plastic brain resident cell in the context of disease. The results obtained point to various clusters of brain metastasis-associated astrocytes as contributors to the progression of metastases and thus therapeutic targets. The function of specific subpopulations of these reactive astrocytes has uncover previously ignored cell-to-cell interactions in particular with CD8+ T cells, which is being translated into novel immunotherapeutic approaches in order to develop more effective strategies against the most frequent brain tumor.

 

Scientific Production
 
Magazine Articles 16
Communications at national conferences 20
Communications at international conferences 39

 

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