Lactylation in Tumor Immune Escape and Immunotherapy: Multifaceted Functions and Therapeutic Strategies

Since its initial identification in 2019, lactylation has emerged as a critical posttranslation modification, attracting substantial research interest due to its diverse roles in biological processes. Lysine lactylation represents a recently characterized posttranslational modification wherein lactate moieties are covalently attached to protein lysine residues through both enzymatic and nonenzymatic pathways. Lactate, a primary glycolytic product, suggests a link between cell metabolism and protein function regulation. In neoplastic tissues, the Warburg effect induces preferential glucose-to-lactate metabolism in cancer cells, establishing hypoxic conditions and elevated lactate concentrations as defining characteristics of the tumor microenvironment. Extensive research has demonstrated lactate's pivotal role in tumor metastasis and patient outcomes, particularly through its influence on tumor immune microenvironment remodeling, although the precise molecular mechanisms remain under investigation. The characterization of lysine lactylation provides a novel framework for understanding these mechanisms and presents innovative opportunities for therapeutic intervention. This review examines the influence of lactylation on the tumor microenvironment and its effect in various malignancies and explores emerging therapeutic strategies, including genetic manipulation, small-molecule inhibitors, clinical pharmaceuticals, and nanoparticle-based approaches, offering new perspectives in cancer treatment.