Samuel Cheshier, MD, PhD, is a pediatric neurosurgeon specializing in treating brain tumors. He and his collaborators recently completed a clinical trial using a unique immune therapy, patient samples, and MRI to track macrophage responses within tumors. The trial looked into a new class of immunotherapies that can be used to stimulate immune cells called macrophages that eat brain tumors.
“When you give patients these immunotherapies, there’s a massive influx of macrophages into the tumor,” Dr. Cheshier said. “Generally, we use monoclonal antibodies to track immune cells because they can bind to and tag them; instead, we’ve repurposed an IV-delivered iron replacement—usually
used for patients with kidney failure or those undergoing chemotherapy who need iron—to look for the macrophages. The macrophages will respond to the immunotherapy, eat the iron nanoparticles, and then go to the tumor, which the MRI will then be able to identify in a noninvasive manner.”
During their laboratory work, Dr. Cheshier and his team have also learned that macrophages from infants are considerably better at eating tumor cells than macrophages from adults. “With this in mind, we’re now exploring why that is the case. There are two proteins, CD32B and LILRB-4, that might be responsible for why a baby’s macrophages can eat tumors better,” Dr. Cheshier said. Both proteins are underexpressed in babies’ macrophages and are overexpressed in adults’ macrophages, so the team is working under the hypothesis that one or both of the proteins may be suppressing the ability of adults’ macrophages to eat tumors. “I’m collaborating with Minna Roh-Johnson, PhD, who works in bioscience, to engineer adults’ macrophages to be more like those found in infants,” he shared.
The pediatrics division is a principal member of the Children’s Brain Tumor Network, the world's largest consortium for brain tumor samples with molecular data integration. “We make the tissue that we collect during our surgeries available to them,” Dr. Cheshier noted, “and in turn, we’re able to use tissue from other centers to study different tumor types and maximize the quality and quantities of the
brain tumor tissue available for advanced scientific research.”
“We currently biobank tumor tissue from nearly every patient, including immediate frozen tissues and living tumor cells frozen in suspended animation, for our own Pediatric Brain Tumor Biorepository and the Children’s Brain Tumor Network,” Dr. Cheshier said. This tumor banking has been instrumental in the development of the Maximal Precision Multi-Omics Program for children with malignant primary brain and spine tumors. In collaboration with Gabor Marth, DSc, and Philip Moos, PhD, Dr. Cheshier has applied the most advanced techniques to analyze each patient's tumor samples with machine-based learning computational platforms to select drugs to which the individual tumor will respond better. These techniques include sequencing the entire genome of the tumor, determining the whole gene expression profiles of thousands of individual tumor cells, and robotics-based multi-drug screens. Dr. Cheshier and his collaborators are in the process of developing a clinical trial that implements this precision drug selection platform for the pediatric patients with brain tumors at Primary Children’s Hospital.