Are childhood cancers different? Understanding the immune response to tumors in pediatric neuroblastoma
Newswise – In patients, a positive response to immunotherapies, a type of medical treatment that helps your body fight cancer, is linked to the immune response to the tumor. Immunotherapy has become a standard treatment for many cancers, but little is known about the immune response to tumors in pediatric patients and how it differs from that in adults.
In a recent study published in the Journal for ImmunoTherapy of Cancer, a team of physician scientists at the University of Chicago Medicine Comprehensive Cancer Center wanted to find out how the immune systems of children with a type of cancer called neuroblastoma respond to tumors. The answer to this question could help in the treatment of pediatric patients.
To ask this question, the researchers examined hundreds of previous cases of neuroblastoma in children. They did a genetic analysis of tumors to gather information about the immune response in each patient. They then looked at how this data related to whether the patients survived cancer.
The genetic analysis of tumors gave the researchers information about the immune cell population in the tumor and how the immune cells responded. Their results revealed dramatically different immune profiles in tumors from different patients and showed that a strong immune response was associated with increased neuroblastoma survival.
The research team, led by Ami Desai, MD, assistant professor of pediatrics at UChicago Medicine, found that patients with tumors with a “T-cell inflamed” profile were more likely to survive. Tumors with this profile had high levels of cytotoxic T cells — the immune cells known for their ability to kill tumor cells.
Their analysis also showed that tumors varied in their amount of “neoantigens,” tumor-specific markers that allow T cells to better target the tumor. Patients with tumors high in neoantigens were also more likely to survive.
In general, children treated for high-risk neuroblastoma had better survival if their tumors were T-cell inflamed and high in neo-antigens.
“New approaches may help us improve treatment options for children with recurrent or difficult-to-treat neuroblastoma,” Desai said. “The correlation of improved childhood survival with certain immune markers shows us that this is a critical area of research, with the potential to expand therapeutic options.”
Susan Cohn, MD, a professor of pediatrics at UChicago Medicine and co-author of the study, explained that the data points to crosstalk between tumor cells and immune cells in the microenvironment that influence response to therapy. Cohn added, “Future studies investigating the genetic profiles of tumor tissue after treatment with immunotherapies may allow us to use these profiles as biomarkers to inform treatment decisions.”
A deeper understanding of the mechanisms driving the presence of T cells and neoantigens in neuroblastoma tumors could provide insight for the development of new immunotherapies to increase the number of T cells in tumors and enhance the antitumor immune response in patients with neuroblastoma. .
Neuroblastoma is a pediatric cancer that usually affects children under the age of five. It is formed from immature nerve cells and usually starts in the adrenal glands. Although neuroblastoma is rare, for high-risk neuroblastoma, only 50% of patients survive after 5 years. UChicago Medicine experts are working to understand and fight this high-risk cancer using advanced treatments.
This research has led to a better understanding of the association between the immune response to tumors and survival in patients with neuroblastoma. The study indicates that in children with high-risk neuroblastoma, immune cells play an important role in determining response to therapy and outcome.
The study, “Immunonomic determinants of the tumor microenvironment correlate with superior survival in high-risk neuroblastoma” was supported by the National Institutes of Health, United States Department of Defense, nonprofit organizations and other donations.
Other authors include Kyle Hernandez, Yuanyuan Zha, Peter Pytel, Thomas Gajewski, and Samuel Volchenboum of the University of Chicago; Riyue Bao and Jason Luke of the University of Pittsburgh’s Hillman Cancer Center; and Stephanie Spranger of the Koch Institute for Integrative Cancer Research at MIT.