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.