Amyloid beta, the hotly contested biomarker for Alzheimer’s disease, could be weaponized by metastasized skin cancer cells to hinder the body’s immune response, according to researchers from NYU Langone Medical Center. But the uncovering of their role also points to a potential therapeutic target in the future.
Part of the evidence established by the researchers was that metastatic melanoma cells in the brain secreted three times as much amyloid beta than in other parts of the body and that the peptide tamped down the immune response responsible for recognizing the dangerous cells.
The study, published March 9 in the American Association for Cancer Research journal Cancer Discovery, homed in on melanoma because it spreads to the brain in up to 75% of patients in advanced stages—more than any other cancer type. It found that on a number of different fronts, melanoma-secreted amyloid beta hindered the body’s ability to fight the dangerous cells.
First, the researchers exposed rats to melanoma with and without amyloid beta to see how the protein (or lack thereof) influences the interaction between melanoma and astrocytes—a type of brain cell. They found that astrocytes exposed to melanoma without amyloid beta had an increase in inflammation signaling compared to when they were exposed to melanoma with amyloid beta, indicating it masks the effect of the spread of cancer cells. Additionally, melanoma-secreted amyloid beta was found to impact microglia, a type of immune cell in the brain, by increasing their anti-inflammatory polarization and hindering their ability to devour cancer cells via phagocytosis.
In other words, researchers found melanoma-secreted amyloid beta helps protect cancer cells in the brain from the body’s immune cells, allowing them to spread.
The findings are the latest to further explore how melanoma spreads or how the immune system can be bolstered to fight it. Prior research indicated that lymph node-specific T cells could have the power to kill melanoma cells before they spread elsewhere. Another study from 2019 discussed how adding anti-platelet drugs to T-cell therapies in mice limited melanoma growth.
For the researchers at NYU, the findings presented an obvious question: Could targeting amyloid beta act as a potential therapeutic for patients with advanced melanoma? The authors found that, in short, possibly, as mice injected with anti-amyloid beta antibodies showed a reduction in metastatic burden.
The findings have the potential to open the clinical floodgates for melanoma given the amount of amyloid beta-targeted antibodies being developed to crack the Alzheimer’s case. For this trial, Eli Lilly’s LY2886721 antibody was used, which was discontinued in a 2013 phase 2 trial for Alzheimer’s due to abnormal liver tests in some of the participants.
“Several therapeutic agents targeting [amyloid beta] have been developed and tested in clinical trials for treatment of Alzheimer’s disease that could potentially be repurposed for treatment of melanoma brain metastasis,” the authors wrote.