Publications by authors named "Levi M Mangarin"
Article Synopsis
- Tumor cells heavily depend on glycolysis for energy, making immunotherapy more effective against tumors with low glycolysis and less lactate dehydrogenase (LDH) activity, leading to better glucose availability for immune cells.* ! -
- Inhibiting LDH reduces glucose uptake and growth in tumor cells while increasing glucose uptake and activity in tumor-infiltrating T cells, improving their ability to kill tumors and counteracting immunosuppression.* ! -
- Combining LDH inhibitors with immune checkpoint therapies shows promising results in controlling cancer progression by enhancing T cell activity and weakening regulatory T cell functions in mouse models of melanoma and colon cancer.* !
MEK inhibitors (MEKi) have shown limited success as a treatment for MAPK/ERK pathway-dependent cancers due to various resistance mechanisms tumor cells can employ. CH5126766 (CKI27) is an inhibitor that binds to MEK and prevents release of RAF, reducing the relief of negative feedback commonly observed with other MEKis. We observed that CKI27 increased MHC expression in tumor cells and improved T cell-mediated killing.
View Article and Find Full Text PDFOnly a subset of cancer patients responds to checkpoint blockade inhibition in the clinic. Strategies to overcome resistance are promising areas of investigation. Targeting glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) has shown efficacy in preclinical models, but GITR engagement is ineffective in controlling advanced, poorly immunogenic tumors, such as B16 melanoma, and has not yielded benefit in clinical trials.
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