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Limited progress has been made over the last 30 years against kid brain tumors, especially those in the thalamus and the pons (Diffuse Intrinsic Pontine Glioma, DIPG), a specific location in the brain. Radiotherapy (RT) is the only treatment available that can prolong the life of children with the most aggressive form of brain tumors. Recently, RT is recognized to activate the immune system against multiple tumors. However irradiated kid brain cancers always regrow which suggest that RT is not activating immunity against these tumors. Understanding why this phenomenon is happening is critical to develop strategies that will exploit the immune stimulation from RT to control and cure brain cancer. The activation of cancer-associated fibroblasts (CAFs) by RT can be responsible for treatment resistance and the lack of immune stimulation of kids brain cancers. Dr. Vanpouille-Box's initial results show that stopping the immunosuppression of CAFs with a fibroblast activating protein alpha (FAP) blocker re-activates the immune system against irradiated pediatric brain tumors. Thus, blocking CAF emerges as a novel approach to prevent brain cancer regrow and to activate immunity in irradiated brain cancer. She proposes to: 1) Define the role of CAF in mice models of pediatric brain cancer 2) Determine the efficacy of CAF and EGFR blockade in irradiated pediatric brain cancer. Dr. Vanpouille-Box and colleagues hope to find that: - CAF stop the immune stimulation of irradiated pediatric brain tumors - blocking CAF immunosuppression works well to reactivate immunity against irradiated brain cancer, especially on the context of epidermal growth factor receptor therapy.

This grant is named for the Pray for Dominic Hero Fund. The fund was established in honor of Dominic Liples who lived with joy. He is remembered for compassion and determination while he faced his own difficult battle with a rare and aggressive brain cancer. The Pray for Dominic fund carries on Dominic's legacy of joy and hope by funding research for high-grade gliomas.