Immunotherapies that target PD-1 have been found to be effective in metastatic melanoma and other cancers, however a large number of patients do not show durable responses. A novel method to determine which patients are most likely to respond positively to immunotherapy has been developed by a team of researchers from the University of Zurich and the University Hospital Zurich (UHZ). Using high-dimensional single-cell mass cytometry, the team was able to identify biomarkers in the blood that indicate whether the therapy is highly likely to be effective even before treatment is commenced.
"White blood cells of patients should be analyzed for these biomarkers when making a decision about immunotherapy. This has the potential to dramatically increase the percentage of patients who will benefit from this type of therapy," reports Burkhard Becher from the Institute of Experimental Immunology at UZH. "At the same time, it makes it possible to directly move on to different therapy modalities in cases where immunotherapy won't work—without losing valuable time."
For the research, which was published earlier this week in Nature Medicine, the researchers examined biomarkers in 40 blood samples from 20 patients, both before and 12 weeks after immunotherapy. They used cytometry by time of flight (Cy-TOF), which analyzes cells for up to 50 different proteins one cell at a time. The researchers were thus able to differentiate every single cell and document its activation status.
After analyzing the cells, the researchers examined the data. "Even before the start of a therapy, we observed a subtle and weak immune response in the blood mediated by cancer, and identified a small subpopulation of white blood cells to coincide with better therapy outcome," says Becher. The team validated their findings using conventional, flow cytometry methods in a second, independent cohort of more than 30 patients.
"Together with comprehensive, precisely structured biobanking, this study represents a major step towards precision medicine," adds Mitch Levesque from UHZ.