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Updated: Jun 16, 2026

Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells
Published on: February 24, 2026
Roles of lactate and lactylation in tumor immune suppression and drug resistance
Jiaqi Li1, Wangji Yang1, Tian Xin1
1West China School of Medicine, West China School of Pharmacy, Department of Thyriod and Breast Surgery, West China School of Public Health, West China Fourth Hospital, Sichuan University, Chengdu, China.
Abstract:
Metabolic reprogramming is a hallmark of cancer, with excessive lactate accumulation driven by aerobic glycolysis profoundly reshaping the tumor microenvironment (TME). Beyond being a metabolic by-product, lactate acts as a signaling metabolite and epigenetic regulator that promotes immune suppression and therapeutic resistance. Lactate-induced acidification impairs immune cell function and reprograms macrophages, T cells, and dendritic cells toward immunosuppressive phenotypes. Moreover, lactate drives lysine lactylation of histone and non-histone proteins, linking metabolic status to transcriptional regulation and oncogenic signaling. Emerging evidence indicates that lactate and lactylation cooperatively enhance tumor survival, invasion, and resistance to chemotherapy, radiotherapy, anti-angiogenic therapy, and immunotherapy. This review summarizes mechanisms of lactate production, transport, and signaling, and discusses therapeutic strategies targeting lactate metabolism, lactylation, and TME acidification, highlighting their potential in precision and combination cancer therapy.
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