Overview

Primary brain tumors, particularly glioblastoma, remain among the most lethal cancers despite decades of advances in surgery, radiation and chemotherapy. Immunotherapies that have transformed outcomes in other cancers have shown limited success in brain tumors. This is largely due to profound tumor heterogeneity, adaptive resistance, and the uniquely hostile metabolic and immunologic landscape of the brain tumor microenvironment.

The Brain Tumor Metabolism and Immunotherapeutics Laboratory, led by Loic P. Deleyrolle, Ph.D., was established to address these unmet challenges by redefining how tumor-immune interactions are studied and therapeutically targeted. Our work focuses on understanding how treatment-resistant tumor cell states and immune cells dynamically coevolve, exchange metabolic resources and adapt under therapeutic pressure, and how these processes can be disrupted to restore durable antitumor immunity.

Special areas of research interest

Our laboratory integrates mechanistic biology, advanced technologies and therapeutic engineering, with emphasis on:

• Treatment-resistant tumor cell states and intratumoral heterogeneity in glioblastoma.
• Immunometabolism, including glucose, lipid and lactate signaling within the tumor microenvironment.
• Tumor-macrophage metabolic crosstalk, lipid trafficking and immune suppression.
• Engineered immune cell therapies, including CAR-T cells, macrophage-based strategies and metabolic switch receptors.
• Single-cell, spatial and functional profiling to resolve tumor ecosystems in patient-derived models.
• Translational platforms linking patient samples, preclinical models and therapeutic development.

Research goals

Our overarching goal is to develop next-generation immunotherapeutic strategies that are rationally designed to function within the metabolic constraints of brain tumors. Specifically, we aim to:

• Define the biological mechanisms that enable tumor cells to survive therapy and evade immune destruction.
• Map metabolic dependencies and vulnerabilities shared between resistant tumor cells and immune populations.
• Engineer immune cells that can sense, exploit or reprogram tumor-derived metabolic signals.
• Translate mechanistic discoveries into actionable therapeutic concepts supported by robust preclinical validation.
• Train the next generation of scientists at the interface of cancer biology, immunology and translational medicine.

Significance to patient care

Our research is driven by a clear clinical imperative: Patients with aggressive brain tumors urgently need therapies that produce meaningful, durable benefits. By directly addressing the mechanisms underlying therapeutic failure, rather than incremental optimization of existing approaches, our work aims to generate immunotherapies that are better matched to the biological reality of brain tumors.

Through close integration with Mayo Clinic's clinical programs, biobanking efforts and multidisciplinary research environment, discoveries from our laboratory are designed to inform future clinical trials, biomarker development and personalized treatment strategies. Ultimately, our goal is to help shift brain tumor care from transient disease control toward sustained, immune-mediated tumor suppression.