In a discovery that could alter treatments of one of the most deadly complications of melanoma, scientists have found a way to reprogram brain immune cells to fight cancer. The study, published today in cancer cells, reveals how manipulating these cells can enhance the effectiveness of existing cancer treatments and potentially expand survival in patients with brain metastases.
Researchers at the Spanish Institute of Neuroscience have identified a mechanism for converting microglia into uninformed accomplices in cancer growth to effective tumor fighters. This transformation occurs by blocking a specific molecular pathway called RELA/NF-κB.
From friends to enemies
Using advanced single-cell analysis and mouse models, the team found that microglia experienced complex identity metastasis during melanoma progression. These immune cells initially target tumor formation and eventually transform allegiance and begin supporting cancer growth.
“We have identified a key signaling pathway, RELA/NF-KB, which reverses the hybrid function of microglia and activates the immune response against tumors,” explained Berta Sánchez-Laorden, the study’s lead investigator.
Enhance the immune response
The study shows that targeting this pathway can not only counteract harmful microglia, but also actively recruit other immune cells to fight cancer. “When we block RELA/NF-KB signaling in microglia, these cells start sending signals to other immune cells, such as cytotoxic T lymphocytes and natural killer cells, which effectively attack tumor cells,” said Dr. The study said F. javierrodríguez Baena. First author.
This finding is particularly important because brain metastases usually have lower immune cell infiltration compared to tumors elsewhere in the body, making them particularly difficult to treat immunotherapy.
Enhance current treatment
Studies have shown that this approach can improve the effectiveness of existing immunotherapy. “Immune checkpoint inhibitors have revolutionized the treatment of melanoma, but not all patients respond well to these therapies,” Sánchez-Laorden noted. “Our study shows that tying them with RELA/NF- KB inhibitors combined can improve their effectiveness in the treatment of brain metastasis.”
The team used patient samples to validate their findings, suggesting that the strategy may be clinically meaningful immediately. This is especially important considering that melanoma is at the highest risk of spreading to the brain in all cancers.
Looking to the future
“This is just the beginning,” said Rodríguez-Baena. “Our next goal is to further explore how this knowledge can be translated into clinical treatment and to evaluate Rela, which has been approved for other indications approved,” said Rodríguez-Baena. The potential of /NF-KB inhibitors.”
This study represents a significant shift in understanding how brain metastases interact with the environment, targeting not only melanoma but also potentially new therapeutic strategies for other cancers that spread to the brain, such as breast and lung cancer.
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