2ⁿᵈ Edition of the Cancer R&D World Conference 2026
Speakers - CRDWC 2025
Fatima Khan
Fatima Khan
- Designation: Cleveland Clinic
- Country: USA
- Title: Metabolic Rewiring of the Tumor Microenvironment: Disrupting LDHA Driven Immunosuppression in Glioblastoma
Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor that creates an immunosuppressive tumor microenvironment (TME), largely driven by tumor-associated macrophages and microglia (TAMs). GBM cells upregulate lactate dehydrogenase A (LDHA), promoting glycolysis and activating key signaling pathways, including ERK-YAP1/STAT3. This metabolic shift triggers the secretion of CCL2 and CCL7, which recruit TAMs into the TME, further enhancing the tumor’s ability to evade immune surveillance. Infiltrating TAMs release LDHA-enriched extracellular vesicles, reinforcing tumor cell metabolism and survival, and contributing to disease progression. Disrupting this LDHA-mediated tumor-TAM crosstalk not only reduces macrophage infiltration but also reprograms the immune response, restoring immune function. Combining this approach with immune checkpoint blockade shows promising synergistic effects, providing a novel therapeutic strategy to reprogram the GBM immune microenvironment and improve patient outcomes. This work highlights the potential of targeting tumor-associated metabolic pathways to enhance the efficacy of immunotherapy in GBM.
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