Work

Lactate and gastric cancer immunotherapy from regulatory mechanisms to therapeutic strategies: a critical review

Year: 2025

Type: article

Abstract: BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer-related mortality globally, with current immunotherapies exhibiting limited therapeutic efficacy owing to the immunosuppressive tumour microenvironment (TME). MAIN BODY: Lactate, a hallmark metabolic by-product of tumour glycolysis, also functions as a critical metabolic driver. By promoting TME acidification, immunosuppression, and epigenetic reprogramming, lactate emerges as a pivotal regulator in reshaping GC immune evasion and therapeutic resistance, while also strongly correlating with chemotherapy resistance. Furthermore, the dysregulated expression of lactate-associated metabolic genes represents a promising therapeutic target. CONCLUSION: This review elucidates the dual roles and clinical value of lactate in gastric cancer as both an energy substrate and a signalling molecule within the tumour microenvironment and positions lactylation as a critical metabolic-epigenetic bridge. We also discuss innovative strategies that integrate lactate metabolism-targeting immune checkpoint inhibitors to overcome therapeutic resistance in GC.

Source: European journal of medical research

DOI: 10.1186/s40001-025-03383-9