AI-guided discovery of the IRF4-PAICS-LDHA axis as a multitarget hub linking tumor metabolism to CD8+ T cell exhaustion in DLBCL
A metabolic pathway controlling immune evasion in aggressive lymphoma responds to existing drugs, suggesting a new combination therapy approach.
An AI-guided integrative analysis of DLBCL single-cell transcriptomics identified the IRF4-PAICS-LDHA metabolic-immune axis as a multi-targetable hub linking glycolytic reprogramming to CD8+ T cell exhaustion and immune evasion. Functional validation showed that metabolic intervention (methotrexate or LDHA knockdown) reversed T cell exhaustion and suppressed tumor growth, suggesting a new combination immunotherapy strategy for DLBCL.
What the study was
- Study design
- Integrative single-cell transcriptomics + ML framework + functional assays + animal model
- Population
- Diffuse large B-cell lymphoma (DLBCL) patient samples + mouse xenografts
- Category
- Treatment Innovation
- Maturity
- Exploratory
- Journal
- NPJ precision oncology
Why it surfaced
Novel ML-identified multi-targetable metabolic-immune axis in DLBCL; NPJ Precision Oncology journal; mixed species model and preclinical stage limit score.
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