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Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review)

  • Authors:
    • Tao Luo
    • Liang Liu
    • Hao Wang
    • Shuai Wen
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, People's Hospital of Ningxiang City, Hunan University of Chinese Medicine, Ningxiang, Hunan 410699, P.R. China
    Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 58
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    Published online on: June 18, 2025
       https://doi.org/10.3892/ijo.2025.5764
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Abstract

Gliomas are the most common primary brain tumors, and exhibit highly heterogeneous and aggressive biological behaviors. Metabolic reprogramming is a hallmark of gliomas, and lactate accumulation serves a critical role in tumor progression. In addition to its traditional role as a metabolic byproduct, lactate has been recognized as a signaling molecule that modifies proteins through lactylation, which is a novel post‑translational modification. Lactate‑induced lactylation of histone and non‑histone proteins is emerging as a key epigenetic and metabolic regulator that influences glioma development, immune evasion, angiogenesis and therapeutic resistance. The present review provides mechanistic insights into protein lactylation, its role in glioma progression and its potential therapeutic implications. Targeting lactate metabolism and lactylation‑modifying enzymes holds promise for improving glioma treatment outcomes.
View Figures

Figure 1

Process of protein lactylation.
Lactate-derived acyl groups are covalently attached to lysine
residues on histones or other proteins. This process is mediated by
several enzymes, including AARS, p300, GCN5, TIP60, KAT8, HDACs and
SIRTs, which regulate the addition and removal of lactyl groups.
The figure was created using BioRender (https://www.biorender.com). AARS, alanyl-tRNA
synthetase; GCN5, general control non-depressible 5; GLUT, glucose
transporter; HDAC, histone deacetylase; KAT8, lysine
acetyltransferase 8; Lac, lactate; LDH, lactate dehydrogenase;
LGSH, L-lactyl coenzyme A (L-La-CoA) and S,D-lactoylglutathione;
MCT1, monocarboxylate transporter 1; SIRT, sirtuin; TIP60,
Tat-interactive protein 60.

Figure 2

Role of protein lactylation in
glioma. Lactate-induced protein lactylation is involved in
progression, invasion, angiogenesis and therapy resistance. The
figure was created using BioRender (https://www.biorender.com). GDF15, growth
differentiation factor 15; H3K18la, histone H3 lysine 18
lactylation; H3K19la, histone H3 lysine 19 lactylation; Lac,
lactate; MLH1, mutL homolog 1; NME1, NME/NM23 nucleoside
diphosphate kinase 1; PTBP1, polypyrimidine tract binding protein
1; TMZ, temozolomide; VE-cadherin, vascular endothelial cadherin;
XRCC1, X-ray repair cross complementing 1; YTHDF2, YTH
N6-methyladenosine RNA binding protein F2.
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Copy and paste a formatted citation
Spandidos Publications style
Luo T, Liu L, Wang H and Wen S: Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review). Int J Oncol 67: 58, 2025.
APA
Luo, T., Liu, L., Wang, H., & Wen, S. (2025). Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review). International Journal of Oncology, 67, 58. https://doi.org/10.3892/ijo.2025.5764
MLA
Luo, T., Liu, L., Wang, H., Wen, S."Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review)". International Journal of Oncology 67.1 (2025): 58.
Chicago
Luo, T., Liu, L., Wang, H., Wen, S."Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review)". International Journal of Oncology 67, no. 1 (2025): 58. https://doi.org/10.3892/ijo.2025.5764
Copy and paste a formatted citation
x
Spandidos Publications style
Luo T, Liu L, Wang H and Wen S: Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review). Int J Oncol 67: 58, 2025.
APA
Luo, T., Liu, L., Wang, H., & Wen, S. (2025). Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review). International Journal of Oncology, 67, 58. https://doi.org/10.3892/ijo.2025.5764
MLA
Luo, T., Liu, L., Wang, H., Wen, S."Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review)". International Journal of Oncology 67.1 (2025): 58.
Chicago
Luo, T., Liu, L., Wang, H., Wen, S."Protein lactylation and immunotherapy in gliomas: A novel regulatory axis in tumor metabolism (Review)". International Journal of Oncology 67, no. 1 (2025): 58. https://doi.org/10.3892/ijo.2025.5764
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