Why Some Brain Tumors Respond to Immunotherapy
Columbia researchers have learned why some glioblastomas—the most common type of brain cancer—respond to immunotherapy. The findings, reported by the CUIMC Newsroom, could help identify patients who are most likely to benefit from treatment with immunotherapy drugs and lead to the development of more broadly effective treatments.
The study, led by Raul Rabadan, PhD, professor of systems biology and biomedical informatics at Columbia University Vagelos College of Physicians and Surgeons and the Herbert Irving Comprehensive Cancer Center, was published online in the journal Nature Medicine.
Fewer than 1 in 10 patients with glioblastoma respond to immunotherapy, which has shown remarkable success in the past few years in treating a variety of aggressive cancers. But there has been no way to know in advance which glioblastoma patients will respond. Like many other cancers, glioblastomas are able to prevent the immune system from attacking cancer cells. Cancers sometimes put the brakes on the immune system by acting on a protein called PD-1. Immunotherapy drugs called PD-1 inhibitors are designed to release those brakes, unleashing the immune system. Given the success of PD-1 inhibitors in other cancers, doctors were hopeful that the immunotherapy drugs would help patients with glioblastoma.
To understand why only a few of these tumors respond to the immunotherapy drugs, Dr. Rabadan’s team took a comprehensive look at the tumor microenvironment—which includes the tumor itself and all of the cells that support it—in 66 glioblastoma patients before and after treatment with PD-1 inhibitors (nivolumab or pembrolizumab). Of these, 17 had a response to the drugs of six months or longer.
Nonresponsive tumors had more mutations in a gene called PTEN, which led to higher levels of macrophages, immune cells that usually help the body fight bacteria and other invaders. But in glioblastoma, the macrophages release a number of growth factors that promote the survival and spread of cancer cells.
Cancer cells in tumors with PTEN mutations were also tightly clustered together, which may prevent immune cells from penetrating the tumor and its microenvironment. Responsive tumors, on the other hand, had more mutations in a signaling pathway called MAPK, which helps regulate essential cellular functions. Read the full article at Newsroom.
Dr. Rabadan's lab at Columbia develops mathematical and computational tools to extract useful biological information from large data sets. In the fall of 2017, he established the Program for Mathematical Genomics at Columbia, a highly interdisciplinary center that connects researchers from the fields of mathematics, physics, computer science, engineering and medicine, with the common goal of solving pressing biomedical problems through quantitative methods and analyses.