Mesothelioma researchers in Japan have discovered that a protein called VISTA, which is best known for helping tumors hide from the immune system, also causes mesothelioma cancer cells to grow from within. In a study published in the British Journal of Cancer, scientists from the Aichi Cancer Center Research Institute and Nagoya University call it a new treatment target for the challenging, asbestos-related disease.
Mesothelioma and the VISTA Protein
Like many other cancers, mesothelioma tumors carry high levels of the VISTA protein. VISTA stands for V-domain Ig suppressor of T cell activation. Like PD-1 and CTLA-4, which the drugs nivolumab and ipilimumab are being successfully used to address, it is an immune checkpoint that keeps T cells from being activated.
Using genetic data from The Cancer Genome Atlas, the researchers found that VISTA levels were higher in mesothelioma patients diagnosed with the epithelioid subtype, which is the most common and most treatable form. Patients diagnosed with the more aggressive sarcomatoid form were found to have higher levels of a related protein called B7-H3.
Mesothelioma Cells Grow Faster With VISTA
In laboratory testing, the scientists found that mesothelioma cells given extra VISTA protein multiplied more quickly, but when researchers suppressed VISTA, the tumor growth slowed in both cell cultures and in mice implanted with mesothelioma tumors. Additional testing showed that VISTA interacts with a signaling protein called RIPK1, boosting the activity of a well-known growth switch called AKT found in many cancers. In other words, VISTA is doing more than shielding the tumor; it is actually helping to fuel it.
The Japanese scientists suggest that drugs that block VISTA could help mesothelioma patients diagnosed with the epithelioid subtype, theorizing that blocking the protein could both release the immune system’s brakes and cut off the internal growth signal. They plan to continue their research, testing drugs that are in development as well as other existing checkpoint drugs or treatments aimed at AKT or RIPK1.
Though this mesothelioma research is early and is currently being done in cell lines and lab animals, it offers promise of future clinical trials to see whether blocking VISTA will slow tumors in people. If you or someone you love has been diagnosed with mesothelioma and would like more information about the resources available to you, the Patient Advocates at Mesothelioma.net are here to help. Contact us today at 1-800-692-8608 to learn more.
