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A team of researchers and pediatric neurosurgeons from the University of Pittsburgh School of Medicine and UPMC Children’s Hospital of Pittsburgh has pioneered a novel approach to profiling brain cancers in children, which could significantly enhance diagnostic capabilities and treatment strategies.
In an article published in Science Translational Medicine, the researchers introduced a diagnostic platform that aims to categorize brain tumors by analyzing the immune system’s responses to cancer. This innovative methodology complements existing microscopic and genetic evaluations of cancer cells, offering the potential to tailor treatments based on the individual immune profiles of patients. This shift could parallel the breakthroughs seen in immunotherapy for childhood leukemias.
Lead author Itay Raphael, Ph.D., a research assistant professor in neurological surgery at Pitt, emphasized the importance of understanding the interplay between immune cell diversity and the various types of brain cancers. He noted that this understanding could lead to the discovery of new therapeutic options in the future.
Brain cancer ranks as the second most prevalent cancer in children, following leukemia, and it remains the most lethal form of pediatric cancer. A range of factors contributes to its severity, including the heterogeneity of brain tumors, their resilience to conventional treatments, and the challenges associated with surgical access. In contrast, advancements in immune-based therapies have driven a significant decline in leukemia-related mortality over recent years by harnessing the body’s own defense mechanisms to boost cancer-fighting T cells.
T cells play a crucial role in recognizing specific antigens on the surface of cancer cells, which signals them to attack and eliminate malignancies while sparing healthy tissue. Upon detecting these targets, T cells become activated and proliferate through clonal expansion, a vital process aimed at eradicating tumors.
Given that brain tumors and their associated antigens can be highly heterogeneous, analyzing the molecular structure of these tumors is key for personalizing patient treatment plans. The study’s innovative approach provides insights into identifying the most effective treatment options by assessing the abundance of T cell surface receptors in the tumor’s microenvironment.
Senior author Gary Kohanbash, Ph.D., an assistant professor of neurological surgery at Pitt, remarked on the significant promise that T cell-based therapies hold for brain cancers, comparable to their success in treating non-brain tumors like leukemia. The study benefitted from an extensive dataset of pediatric tumor samples and advanced bioinformatics tools, enabling researchers to explore how T cell immune responses and clonal expansion can serve as markers for treatment classification and prognostic evaluation, independent of other diagnostic methods.
As part of their research, the team analyzed nearly 1,000 pediatric brain tumor samples collected via the Children’s Brain Tumor Network (CBTN), a collaboration of 35 medical centers across the United States and beyond. This investigation was the first to examine the T cell clonal repertoire and its expansion within this specific group of samples.
The findings indicate that more aggressive tumor variants tend to show reduced T cell expansion compared to their less aggressive counterparts, implying that the assessment of T cell clonality could provide valuable prognostic information across various tumor types. Furthermore, understanding T cell responses may reveal exploitative therapeutic targets related to the antigens present on tumor cell surfaces, paving the way for the development of cancer-antigen peptide immunotherapies.
Co-author Ian Pollack, M.D., a distinguished professor of neurological surgery at Pitt and a founding principal investigator of CBTN, expressed hopes that clonal T cell expansion will become a standard element in pediatric cancer diagnosis. He noted UPMC Children’s Hospital’s commitment to advancing brain tumor research and creating new, life-saving treatments, suggesting that this landmark study represents a significant evolution in the field’s approach to pediatric tumors.
Additional contributors to the research included Zujian Xiong, Chaim Sneiderman, Rebecca Raphael, M.S., Sydney Jackson, ReidAnn Sever, Sarah Vincze, Baoli Hu, Ph.D., Sameer Agnihotri, Ph.D., Jan Drappatz, M.D., Taylor Abel, M.D., Shikhar Uttam, Ph.D., Michal Nisnboym, M.D., Yael Nechemia-Arbely, Ph.D., Udai Kammula, M.D., Jeremy Rich, M.D., Thomas Pearce, M.D., Ph.D., Maria Chikina, Ph.D., and Dhivyaa Rajasundaram, Ph.D., all affiliated with Pitt, among others.
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