SUMMARY
Loic P. Deleyrolle, Ph.D., is a neuroscientist with specialization in neuro-onco-immunology. Dr. Deleyrolle integrates principles of neuroscience, tumor biology and immunometabolism to study malignant brain tumors. He researches the metabolic and immunologic mechanisms that drive brain malignancies, including high-grade glioma.
Dr. Deleyrolle investigates how tumor metabolism and immune cell function intersect within the tumor microenvironment to promote heterogeneity, immune suppression and treatment resistance. He and his research team use integrative multi-omics approaches, patient-derived models and metabolic engineering to develop innovative immunometabolic therapies. Their work focuses on reprogramming tumor-immune interactions and improving the effectiveness of treatments for malignant brain cancers.
Focus areas
- Investigating metabolic communications between tumor cells and immune cells within the brain tumor microenvironment. The glioma microenvironment is complex and heterogeneous, which impedes both the understanding of glioma biology and the elaboration of efficient clinical interventions. The focus of this research project is to mechanistically understand the nature of metabolic communications that take place in the tumor microenvironment, especially between immune-suppressive cells and tumor cells that resist therapy. This research also tests the therapeutic effect of disrupting these interactions to treat brain tumors. The long-term goal of this project is to translate the information gained from research into strategies that are useful as clinical therapies to improve outcomes.
- Engineering metabolically enhanced immune cell products to overcome nutrient competition and immunosuppression in the brain tumor microenvironment. The metabolic switch observed in high-grade glioma leads to increased glycolysis in tumor cells and impacts the tumor microenvironment. This in turn acts as a major barrier for successful targeting of cancer by antitumor immune cells such as T cells. The tremendous increase in tumor glucose consumption imposes a great metabolic pressure on T cells, which experience glucose restriction. The overarching goal of this project is to manipulate the metabolic fitness of chimeric antigen receptor-modified T cells to ameliorate their tumoricidal activity in the context of immunotherapy to treat high-grade gliomas.
- Reprogramming immune-tumor metabolic interactions, including leveraging lactate signaling to augment antitumor immunity. This research project aims to overcome tumor-induced immunosuppression. This is done by engineering T cells to express a chimeric metabolic switch receptor that converts the immunosuppressive signal of tumor-derived lactate into a stimulatory one. This process would then stimulate T-cell glycolysis and effector function.
- Advancing RNA-based adoptive T-cell therapies targeting treatment-resistant persister cells to prevent recurrence in high-grade glioma. The severity of glioma is related to pathogenic drivers that are tolerant of conventional therapies. Dr. Deleyrolle and his team discovered a specific pool of cancer stem cells that show greater treatment resistance and tumorigenicity. Their work leverages the ability to purify these cells to develop a novel targeted immunotherapy strategy. This strategy is based on the use of immunogenic antigens isolated from the clinically relevant population as activators of immune effectors in the context of adoptive cell therapy to prevent recurrence in high-grade glioma.
- Teaching and mentoring. In addition to conducting research in the lab, Dr. Deleyrolle is engaged in teaching and mentoring the next generation of scientists in the field of cancer biology, immunology and metabolism.
Significance to patient care
Patients with brain cancer typically have limited treatment options. Dr. Deleyrolle's research is working to change this by creating new treatments that use the body's own immune system to find and fight the cancer. His team studies how brain tumor cells change their metabolism to grow and hide from the immune system. The team then designs ways to reprogram immune cells to function better within the tumor environment. The goal is to create safer and better treatments that improve survival and quality of life.
Professional highlights
- Member, Study Section, Advancing Therapeutics A, National Institutes of Health, 2025-present.
- Member, Study Section, Glioblastoma Research Program, Department of Defense, 2024-present.
- Frontiers:
- Associate editor, Neuro-Oncology and Neurological Oncology specialty section, Frontiers in Neurology, 2022-present.
- Associate editor, Neuro-Oncology and Neurological Oncology specialty section, Frontiers in Oncology, 2022-present.
- Review editor, Stem Cell Research specialty section, Frontiers in Cell and Developmental Biology, 2022-present.
- University of Florida:
- Chair, Scientific Advisory Group, Interdisciplinary Center for Biotechnology Research — Flow Cytometry and Microscopy Core, 2021-2024.
- Best Mentor Award, Center for Inclusion and Multicultural Engagement: University Multicultural Mentor Program, 2022.
- Best Project Award, Southeastern Brain Tumor Research Meeting, Southeastern Brain Tumor Foundation, 2023.
- St. Baldrick's Scholar, St. Baldrick's Foundation, 2019.