ArticleCell proliferation2023
Lactate trafficking inhibition restores sensitivity to proteasome inhibitors and orchestrates immuno-microenvironment in multiple myeloma.
Article in Cell proliferation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 20 citations in OpenAlex.
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Electrorotation as a tool for the dielectric characterization of tumor plasma cells in multiple myeloma.Scientific reports · 2026Article
- Mechanisms and intervention strategies of microenvironment-mediated drug resistance in multiple myeloma.Cancer cell international · 2026Review
- Spatiotemporal control of mitoribosome-mediated metabolic reprogramming in cancer: implications for heterogeneity and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Metabolic reprogramming in tumor-associated cells of hematologic malignancies: mechanisms, crosstalk networks, and therapeutic implications in the tumor microenvironment.Frontiers in immunology · 2026Review
- Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming.Experimental hematology & oncology · 2025Review
- Mitochondrial fission factor drives an actionable metabolic vulnerability in multiple myeloma.Haematologica · 2025Article
- Review
- Myeloid cells: key players in tumor microenvironments.Frontiers of medicine · 2025Review
- Lactate accumulation promotes immunosuppression and fibrotic transformation of bone marrow microenvironment in myelofibrosis.Journal of translational medicine · 2025Article
- Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies.Theranostics · 2025Review
- miR-326 overexpression inhibits colorectal cancer cell growth and proteasome activity by targeting PNO1: unveiling a novel therapeutic intervention strategy.Scientific reports · 2024Article
- Fueling CARs: metabolic strategies to enhance CAR T-cell therapy.Experimental hematology & oncology · 2024Review
- Adipocytes and metabolism: Contributions to multiple myeloma.Journal of bone oncology · 2024Article
- Effects of Lactate Transport Inhibition by AZD3965 in Muscle-Invasive Urothelial Bladder Cancer.Pharmaceutics · 2023Article
- Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers.Biomolecules · 2023Review
- MacroH2A1.1 as a crossroad between epigenetics, inflammation and metabolism of mesenchymal stromal cells in myelodysplastic syndromes.Cell death & disease · 2023Article
- Article
- Lactate trafficking inhibition restores sensitivity to proteasome inhibitors and orchestrates immuno-microenvironment in multiple myeloma.Cell proliferation · 2023Article
- Metabolic changes underlying drug resistance in the multiple myeloma tumor microenvironment.Frontiers in oncology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Metabolic changes of malignant plasma cells (PCs) and adaptation to tumour microenvironment represent one of the hallmarks of multiple myeloma (MM). We previously showed that MM mesenchymal stromal cells are more glycolytic and produce more lactate than healthy counterpart. Hence, we aimed to explore the impact of high lactate concentration on metabolism of tumour PCs and its impact on the efficacy of proteasome inhibitors (PIs). Lactate concentration was performed by colorimetric assay on MM patient's sera. The metabolism of MM cell treated with lactate was assessed by seahorse and real time Polymerase Chain Reaction (PCR). Cytometry was used to evaluate mitochondrial reactive oxygen species (mROS), apoptosis and mitochondrial depolarization. Lactate concentration resulted increased in MM patient's sera. Therefore, PCs were treated with lactate and we observed an increase of oxidative phosphorylation-related genes, mROS and oxygen consumption rate. Lactate supplementation exhibited a significant reduction in cell proliferation and less responsive to PIs. These data were confirmed by pharmacological inhibition of monocarboxylate transporter 1 (MCT1) by AZD3965 which was able to overcame metabolic protective effect of lactate against PIs. Consistently, high levels of circulating lactate caused expansion of Treg and monocytic myeloid derived suppressor cells and such effect was significantly reduced by AZD3965. Overall, these findings showed that targeting lactate trafficking in TME inhibits metabolic rewiring of tumour PCs, lactate-dependent immune evasion and thus improving therapy efficacy.
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