Merkel cell carcinoma is a rare, aggressive form of skin cancer usually caused by Merkel cell polyomavirus. The virus, which most people carry, is typically harmless. In 2,500 Americans each year, the viral genome becomes incorporated into skin cells, leading to the development of Merkel cell cancer. The tumors typically grow rapidly and metastasize quickly, meaning it is very important to evaluate disease severity and understand the body’s response to these tumors. Haroldo Rodriguez, a graduate student working under Justin Taylor, PhD, Resident Member of the Beirne B. Carter Center for Immunology Research and Associate Professor of Medicine, recently published a preprint of his research, which correlates immune activity to patient outcomes in this disease.
B cells are a type of white blood cell that primarily produce antibodies, which help coordinate the body’s immune response by marking viruses, bacteria, and cancer cells for destruction. In Merkel cell carcinoma, the viral component of the disease produces a protein, called the T-antigen. “They’re present in all tumor cells from Merkel cell patients,” Rodriguez explains. “They’re the perfect key because the proteins don’t mutate, generate a strong immune response, and are ubiquitous.” Rodriguez and Taylor gathered samples from patients who had different disease outcomes and analyzed the RNA of individual cells to see if there was a difference in B cell activity targeting the T-antigens between patients who survived and those who did not. “We could accurately predict disease outcome in 19 out of 19 cases by analyzing T-antigen-specific B cells,” says Taylor. “In contrast, when we analyzed larger populations of B cells in the same samples, our predictive ability diminished.”
The team, comprised of 37 researchers across UVA, the University of Washington in Seattle, and Fred Hutchinson Cancer Center, found that if patients had B cells inside Merkel cell tumors that specifically targeted T-antigens, they were much more likely to survive after treatment. Rodriguez, who spearheaded the project, was instrumental in keeping the research patient oriented. “He was the one who pushed to make sure we were going to predict outcomes and stratify patients. He kept us focused on the right thing,” recalls Taylor. For his part, Haroldo is particularly proud of the mentorship he was able to provide junior colleagues throughout the project. “I mentored Allison Remington, Rian Alam, and Macy Gilmour, and all three of them have work published in the paper,” he says.
Rodriguez and Taylor hypothesize that these B cells help the body more effectively target and kill the cancer cells. Future work will explore the mechanism by which this occurs using newly developed mouse models. The ongoing collaboration between UVA, UW, and Fred Hutch is supported by an NIH P01 grant in which Taylor is a project leader.