Effect of CD47 on the Tumor Microenvironment in Diffuse Midline Glioma, a Fatal Pediatric Brain Tumor
Abstract
Project Narrative: Brain tumors (gliomas) are responsible for more childhood deaths and the greatest number of years of potential life lost than any other type of cancer. Despite advances in surgery, radiation, and chemotherapy, diffuse midline gliomas (DMG), are among the most aggressive of these tumors and are 100% fatal. New treatment methods (therapeutics) using the immune system (which is composed of cells that are involved in fighting infection), called immunotherapies, offer promise for treating brain tumors in children. However, in order to use immunotherapy in childhood glioma, it is important that we understand how the immune system responds to these tumors, also known as the tumor immune microenvironment. As radiation is the mainstay therapy for DMG, understanding how radiation affects the immune microenvironment – and especially microglia, the most abundant immune cell in the brain – is critical. The results of the proposed studies will bring us closer to successful treatment strategies and combination therapeutics using radiation and immunotherapy for pediatric brain tumors. Specifically, we find that radiation increases CD47, a don’t eat me signal given off by the tumors that allows them to escape immune attack. We can use an immunotherapy against CD47 during and after radiation to improve outcomes in these devastating diseases. Career Development: The Principal Investigator (PI) for this study is currently an Assistant Professor of Pediatrics in the Division of Pediatric Hematology/Oncology at Columbia University Irving Medical Center. She completed her clinical training in Pediatric Oncology and also completed research training as a postdoctoral fellow in Immuno-oncology/Immunotherapy and Precision Medicine. During her training she successfully completed multiple projects leading to six first-author publications evaluating the tumor immune microenvironment in adult tumors, including brain cancer. She also completed an advanced degree, Master of Science in Patient Oriented Research in May 2020. Her training thus far has provided a strong base in clinical trial development, biomedical statistics, epidemiology, and grant writing while also improving her approach to scientific study. This proposal presents a research and career development program focused on evaluating the CD47/SIRPa pathway, especially in response DMG, a fatal pediatric brain tumor. The outlined proposal builds on the candidate’s previous research in immune microenvironment and immunotherapy and integrates two new domains of expertise represented by her mentor team with career guide, Dr. Peter Canoll and co-mentor Dr. Raul Rabadán including mechanistic evaluation of preclinical models and computational analysis of immune cells. To pursue her long-term goal of researching pediatric brain tumors as an independent physician scientist, she has identified several gaps in her training and put together a strong Career Development plan that will address these gaps with the help of her mentors and advisory committee. Impact: The median survival of a child with DMG is 9-15 months. Thus, a diagnosis of this cancer in the child of a military member will certainly impact mission readiness as there is not much time to spare once the tumor has been identified. Further, DMG, being one of the most devastating of pediatric brain tumors, will sacrifice the health and well-being not only of the child but also their military family. This Department of Defense – Career Development Award will improve the use of therapeutics, specifically advancing the use of immunotherapy for DMG. The PI is already engaged directly with cutting edge pediatric cancer and immuno-oncology researchers in committees and working groups which will help to make the findings from this proposal directly available to patients as soon as the research is complete.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310570
Entities
People
- Robyn Gartrell
Organizations
- Columbia University
- United States Army