Certainly! Here is teh content you requested:
Immune Microenvironment of Brain Metastases—Are Microglia and Other … Clinical trials in melanoma brain metastases with combined PD-1/CTLA-4 blockade showed ~50% intracranial response rate (36 … Depletion of microglia and macrophages by treatment with PLX3397, an inhibitor of colony stimulating factor-1 receptor (CSF-1R), reduced the total number and mean size of the brain metastases by 83 and 65%, respectively
URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC6710386/
The Role of Microglia in Brain Metastases: Mechanisms and … – PubMed Brain metastases and related complications are one of the major fatal factors in cancer. Patients with breast cancer, lung cancer, and melanoma are at a high risk of developing brain metastases. However, the mechanisms underlying the brain metastatic cascade remain poorly understood. Microglia, one …
URL: https://pubmed.ncbi.nlm.nih.gov/37307835/
The Vicious Cycle of Melanoma-Microglia Crosstalk: Inter-Melanoma… SOCS3-Expressing Microglia Cells in Melanoma Brain Metastases Are Activated . We next asked if the gene signature of MCM-treated microglia is expressed by microglia that infiltrates MBM in vivo. … The treatment of microglia-YDFR.CB3, microglia-M12.CB3, or microglia-M16.CB3 spheroids with rIL-6 resulted in an increase in the quantity of …
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1…oal is to further explore how this knowledge can be translated into clinical treatments and evaluate the potential of Rela/NF-kB inhibitors already approved for other indications”, says Rodríguez-Baena.
The team collaborated with the Cellular Plasticity and Neuropathology lab at IN, led by researcher José López-Atalaya, an expert in microglia and sequencing data analysis, as well as with the team of Professor Gema Moreno Bueno from the Sols-Morreale Biomedical Research institute (IIBM-CSIC-UAM) and the MD Anderson Foundation (both in Madrid), who provided patient samples.
This research was made possible thanks to funding from the melanoma Research Alliance, the FERO Foundation, the Spanish State Research Agency – Ministry of Science, Innovation, and Universities, and the Carlos III Health Institute (ISCIII), among others.
Source: Miguel Hernández University (UMH) in Elche
Journal reference: Rodriguez-Baena, F. J.,et al. (2025). Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases. Cancer Cell. doi.org/10.1016/j.ccell.2025.01.008.
Immune Microenvironment of Brain Metastases—are Microglia the Key?
Table of Contents
Recent research has highlighted the critical role of the immune microenvironment,particularly microglia,in the advancement and treatment of brain metastases,especially in cases of melanoma. This interview delves into the latest findings and their implications for cancer therapy.
Introduction to microglia in Cancer
Editor: Can you start by explaining what microglia are and their role in the context of cancer, particularly brain metastases?
Dr. Francisco Rodríguez-Baena: Microglia are the resident immune cells of the central nervous system. They function to maintain brain homeostasis and respond to any disturbances, including the presence of cancer cells. In the context of brain metastases, microglia can be activated, which can either help in clearing the cancer cells or, conversely, aid tumor progression.
Brain Metastases: Prevalence and Mechanisms
Editor: What are some of the major cancers that lead to brain metastases, and how do you think the underlying mechanisms contribute to these metastases?
Dr. Rodríguez-Baena: Brain metastases are most commonly seen in cases of breast cancer, lung cancer, and melanoma. The mechanisms by which these tumors metastasize to the brain remain poorly understood, but it appears microglia may play a significant role in facilitating or hindering this process.
Depletion of Microglia
Editor: You mentioned a study involving PLX3397, an inhibitor of the colony-stimulating factor-1 receptor (CSF-1R). How does this relate to reducing brain metastases?
Dr. Rodríguez-Baena: Our research showed that treatment with PLX3397, an inhibitor of the CSF-1R, led to an 83% reduction in the total number and a 65% reduction in the mean size of the brain metastases. This suggests thating microglia and macrophages can significantly impede tumor growth and spread in the brain.
Mechanisms of Microglial Activation
Editor: Can you describe how microglia are activated in melanoma brain metastases and the implications of this activation?
Dr. rodríguez-Baena: In melanoma brain metastases, microglia are activated to express SOCS3, which can participate in a vicious cycle that promotes tumor growth. Understanding these mechanisms can help in developing targeted therapies to inhibit this pathway.
Role of Interleukins
Editor: What role do interleukins play in the crosstalk between microglia and melanoma cells?
Dr. Rodríguez-Baena: Interleukins, such as IL-6, can increase the quantity of activated microglia. This interplay between microglia and melanoma cells creates an inflammatory habitat that further propels tumor growth.
Promising Directions in Research
Editor: Based on the research, what are some of the potential clinical applications and future directions in this area?
Dr. Rodríguez-Baena: Our goal is to explore how the knowledge we’ve gained can be translated into clinical treatments. The use of Rela/NF-kB inhibitors,which are already approved for other conditions,might be a promising avenue to enhance antitumor immunity and immunotherapy response in melanoma brain metastases.
Collaborations and Funding
Editor: Can you tell us more about the collaborations and funding sources that enabled this research?
Dr. Rodríguez-Baena: We collaborated with the Cellular Plasticity and Neuropathology lab at the Institute of neurosciences in Alicante, led by researcher José López-Atalaya, and with Professor Gema Moreno Bueno’s team at the Sols-morreale Biomedical Research Institute. Funding came from various sources, including the Melanoma Research Alliance and the FERO foundation.
Conclusion
Editor: summarizing,what are the main takeaways from your research?
dr. Rodríguez-Baena: The key takeaway is that microglia play a crucial role in the development of brain metastases. The clinical trials and research findings indicate that targeting these cells, potentially thru inhibiting CSF-1R or using Rela/NF-kB inhibitors, could significantly improve outcomes for patients with melanoma brain metastases.
