Pitt researchers are developing a new way to profile pediatric brain tumors

Pitt researchers are developing a new way to profile pediatric brain tumors

Researchers and pediatric neurosurgeons at the University of Pittsburgh School of Medicine and UPMC Children's Hospital in Pittsburgh developed a new way to profile brain cancers in children, paving the way for improved diagnostics and treatments.

Today inScience Translational MedicineResearchers describe a diagnostic platform that could classify brain tumors based on the body's immune response. This approach, complemented by traditional microscopic and genetic cancer cell analyses, represents the opportunity to tailor cancer therapies to the patient's unique immune response and capitalize on the success of immunotherapies that revolutionized the treatment of childhood leukemias.

Understanding how the repertoire of immune cells fits into the diverse landscape of brain cancers may help us find new therapies in the future. “

Itay Raphael, Ph.D., senior author, research assistant professor of neurological surgery at Pitt

Brain cancer is the second most common cancer in children after leukemia, and it is also the deadliest. This is due to a constellation of factors: brain tumors are diverse, resistant to treatment and often difficult to access. On the other hand, the sharp reduction in deaths from leukemia in recent decades is due in part to the enormous success of immune-based therapies that exploit the body's intrinsic protective mechanisms by expanding the pool of cancer-fighting white blood cells called T cells.

T cells are precisely tuned to recognize molecules on the surface of cancer cells – called antigens – as signals to attack and delete tumor cells while remaining intact. When T cells find a target on the tumor cell surface, they become activated and quickly double their numbers in a process called clonal expansion to erase the cancer.

Because of the way different brain tumors and their antigens are, understanding the molecular composition of the tumor can help clinicians personalize treatment for each patient. Similarly, the new study's complementary approach may help determine the best treatment option by identifying which T cell surface receptors are most prevalent in the tumor's surroundings.

“The success of cell-based T-based therapies for non-brain tumors, including childhood leukemias, suggests tremendous potential for brain cancers,” said senior author Gary Kohanbash, Ph.D., assistant professor of neurological surgery at Pitt. “Having access to an unprecedented dataset of pediatric tumors and new bioinformatics tools has allowed us to explore how T cell immune response and clonal expansion can be used as markers for treatment classification and prognosis independent of other diagnostic tools.”

As part of the study, researchers presented nearly 1,000 pediatric brain tumor samples collected by the Children's Brain Tumor Network (CBTN), a medical research consortium of 35 medical centers across the country and globally. The study first looked at the clonal T cell repertoire and expansion in this sample group.

The group observed that very aggressive tumor types are associated with lower T cell expansion than less aggressive ones, suggesting that clonality may inform patient outcomes across tumor types. On the other hand, studying the T cell response may shed light on how antigens on the surface of cancer cells can be used therapeutically, providing avenues for the development of cancer antigen-peptide immunotherapy.

“Ultimately, we hope for a future in which clonal T cell expansion is incorporated into the diagnosis of pediatric cancers,” said co-author Ian Pollack, MD, distinguished professor of neurological surgery at Pitt and a founding institutional principal investigator of CBTN. “UPMC Children’s Hospital is committed to supporting brain cancer research and developing new life-saving treatments, and we believe this landmark study represents a fundamental shift in the way the field will consider pediatric tumors in the future.”

Other authors of the study include Zujian Xiong, Chaim Sneiderman, Rebecca Raphael, MS, Sydney Jackson, Reidann Sever, Sarah Vincze, Baoli Hu, Ph.D. Yael Nechemia-arbel, Ph.D., Udai Kammula, MD, Jeremy Rich, MD, Thomas Pearce, MD, Ph.D., Maria Chikina, Ph.D., and Dhivyaaaaaaaaaaaaaaaaaaaaaaa-Ph.D., all from Pitt, all from Pitt.

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