LDHA-driven lactate metabolism promotes MDSC activation and immunosuppressive microenvironment in prostate cancer - PubMed
4 hours ago
- #Lactate Metabolism
- #Immunosuppression
- #LDHA
- LDHA-driven lactate metabolism in prostate cancer promotes MDSC activation and an immunosuppressive microenvironment.
- LDHA-high tumors show increased lactate production, immune exclusion, and infiltration of PMN-MDSCs co-localized with LDHA-positive regions.
- Lactate uptake via MCT1 enhances PMN-MDSC differentiation and upregulates Arg1 and NOS2, leading to T cell suppression.
- Genetic LDHA ablation in mice reduces PMN-MDSC infiltration, restores CD8+ T cell activity, and inhibits tumor growth.
- Pharmacological LDHA inhibition with FX-11 synergizes with anti-PD-L1 therapy, achieving durable tumor regression.