The Exosome‐Lactate‐Lactylation Axis: A Metabolic‐Epigenetic Circuit Driving Tumor Immune Evasion

Lactylation, as a post-translational modification, plays a role in tumor proliferation, metabolism, and the remodeling of the tumor microenvironment (TME). Emerging studies have revealed that exosomes regulate lactate metabolism by delivering functional molecules (such as lncRNAs, metabolic enzymes, etc.) thereby driving protein lactylation and establishing a novel intercellular communication mechanism. Furthermore, acidic microenvironments induce the release of immunosuppressive exosomes, amplifying immune evasion. Here, we summarize the current understanding of lactylation and exosome regulation in the TME and their impact on immune evasion. We explore the pivotal role of the "exosome-lactate-lactylation" axis in tumor metabolic reprogramming, metastasis, and immunosuppression, proposing targeted strategies against this axis.

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Publication Details

Journal
Comprehensive physiology
Published
2026-03-16
DOI
https://doi.org/10.1002/cph4.70114
Primary Topic
Cancer, Hypoxia, and Metabolism
Type
article
Field-Weighted Citation Impact
0.00
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article

The Exosome‐Lactate‐Lactylation Axis: A Metabolic‐Epigenetic Circuit Driving Tumor Immune Evasion

Ye Yuan, Zhen Zhang, Yihai Shi, Yuan Chen
Comprehensive physiology
Cancer, Hypoxia, and Metabolism
article

The Exosome‐Lactate‐Lactylation Axis: A Metabolic‐Epigenetic Circuit Driving Tumor Immune Evasion

Ye Yuan, Zhen Zhang, Yihai Shi, Yuan Chen
article en

Abstract

Lactylation, as a post-translational modification, plays a role in tumor proliferation, metabolism, and the remodeling of the tumor microenvironment (TME). Emerging studies have revealed that exosomes regulate lactate metabolism by delivering functional molecules (such as lncRNAs, metabolic enzymes, etc.) thereby driving protein lactylation and establishing a novel intercellular communication mechanism. Furthermore, acidic microenvironments induce the release of immunosuppressive exosomes, amplifying immune evasion. Here, we summarize the current understanding of lactylation and exosome regulation in the TME and their impact on immune evasion. We explore the pivotal role of the "exosome-lactate-lactylation" axis in tumor metabolic reprogramming, metastasis, and immunosuppression, proposing targeted strategies against this axis.

Comprehensive physiologyVol. 16(2)
University of Shanghai for Science and Technology (CN), Second Military Medical University (CN), Fuyang Maternity and Child Health Care Hospital (CN), Guangdong Academy of Medical Sciences (CN), Shanghai Pudong New Area Gongli Hospital (CN)
Openalex Percentile: Top 20%
Cancer, Hypoxia, and Metabolism
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