ArticleMedical oncology (Northwood, London, England)2026
Spatially resolved lactate-glycolysis transcriptional programs are associated with neutrophil-enriched immune remodeling in lung adenocarcinoma.
Article in Medical oncology (Northwood, London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Metabolic reprogramming characterized by enhanced glycolysis and lactate production plays a critical role in tumor progression and immune regulation. However, the cellular distribution and spatial organization of lactate-glycolysis activity within the lung adenocarcinoma (LUAD) microenvironment remain incompletely understood. We integrated single-cell RNA sequencing, spatial transcriptomics, and bulk transcriptomic datasets from TCGA and GEO cohorts to characterize lactate-glycolysis-associated metabolic heterogeneity in LUAD. AUCell-based scoring was used to quantify metabolic activity at single-cell resolution. Associations with immune infiltration and clinical outcomes were evaluated, and key findings were validated using spatial transcriptomics, quantitative PCR, and immunohistochemistry. Cells exhibiting high lactate-glycolysis activity were predominantly enriched in fibroblasts and neutrophils, indicating that this metabolic program extends beyond malignant cells. A metabolism-associated gene signature, comprising RPS2, GAPDH, and LDHA, was consistently correlated with immune remodeling and an unfavorable prognosis. Spatial transcriptomics further revealed the co-localization of GAPDH and LDHA with neutrophil-enriched regions. These findings were supported by experimental validation in clinical specimens. Our study reveals that lactate-glycolysis reprogramming in LUAD is spatially structured and closely associated with neutrophil-enriched immune remodeling. This metabolism-associated immune regulatory pattern provides insight into the organization of the tumor microenvironment and may have implications for metabolic- and immune-oriented therapeutic strategies in lung adenocarcinoma.
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