ArticleOncology research2026
Lactic Acid Drives ESM1 to Attenuate DNA Damage and CD8+ T Cell Infiltration in Cancer.
Article in Oncology research, 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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9 authors.
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Abstract
Background: Lactate, as a critical byproduct of tumor metabolic reprogramming, plays an important role in DNA damage repair and tumor immune infiltration. This work aims to elucidate the molecular mechanisms by which lactate promotes tumor DNA damage repair (DDR) and subsequent immune evasion. Methods: Hepatocellular carcinoma (HCC), lung adenocarcinoma (LUAD), and ovarian cancer (OC) cells with cisplatin-induced DNA damage were treated with lactate at a concentration gradient, Endothelial cell-specific molecule 1 (ESM1) shRNA, ESM1 overexpression plasmid, or the Protein Kinase B (AKT) Serine/Threonine Kinase 1 (Akt1) inhibitor LY294002. Proliferation, apoptosis, and DNA damage levels were assessed using 5-ethynyl-2 Results: This study demonstrates that lactate increases ESM1 mRNA and protein expression in a concentration-dependent manner and reduces DNA damage in tumor cells. Lactate suppresses DDR by activating the Akt1 signaling pathway via ESM1 and further inhibits the cGAS pathway, thereby downregulating the transcription of chemokines and pro-inflammatory factors. Conclusion: In summary, lactate activates the Akt1-Murine Double Minute 2 (MDM2)-p53 pathway via ESM1 to suppress DDR, while the reduction of DDR-generated dsDNA inactivates the cyclic GMP-AMP synthase-Stimulator of Interferon Genes (cGAS-STING) pathway, thereby inhibiting CD8+ T cell immune infiltration.
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