Microglia, macrophages

Related projects 

Publications 

STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis.

Priego N et al. Nature Medicine. (2018).

Link to Publication

 

The potential of astrocytes as immune modulators in brain tumors

Priego N and Valiente M. Frontiers in Immunology. (2019).

Link to Publication

 

Protocol to generate murine organotypic brain cultures for drug screening and evaluation of anti-metastatic efficacy

Lucía Zhu, Lauritz Miarka, Patricia Baena, María Perea-García, Manuel Valiente. STAR Protocols (2023)

Link to publication

Multicolor immunofluorescence labelling the complexity of resident (microglia) and peripheral (BMDM) macrophages including an additional marker indicative of the pro-metastatic behavior of some of them. Uncovering this molecular heterogeneity, its contribution to brain metastasis progression and its translation to potential new therapeutic approaches is part of our ongoing projects.

Being both resident cells (microglia) and cells infiltrating from peripheral circulation (bone marrow-derived macrophages, BMDM) they create an ecosystem that only appear in the presence of a brain damage, such as brain metastasis. BMDM will never get into the brain unless it is altered. Once there together with the microglia they are supposed to help keeping the function of the brain intact defending it from the invasive tumor, however what happens it is quite the opposite as time progresses. Microglia/ macrophages becomes important contributors to brain metastasis local progression.

We are trying to identify the biology of macrophage/ microglia rewiring in the contect of brain metastasis. A lot has been done already in the field but we are particularly interested in how the cell behavior is influence by a wider cellular network of cancer and non-cancer cells.

We have established a connection between microglia/macrophages and astrocytes by which the reactive glial cell activates a pathway in microglia/macrophages with a remarkable influence on putting them to work for the metastasis.

We are digging as deep as possible in this signalling pathway within microglia/macrophages not only to understand the underlying biology but to explore whether we can target it, thus, aiming to impair the microenvironment corsstalk we think is critical to impair the formation of a pro-metastatic environment in the brain.

Why are microglia/macrophages linked to all brain disorders, including brain metastasis?

We are deconstructing this signalling pathway within microglia/macrophages not only to understand the underlying biology but to explore whether we can target it. We hypothesize that impairing the microenvironment crosstalk is critical to impair the formation of a pro-metastatic environment in the brain.