Exploring the mechanisms of mutual influence between lactylation and macrophage polarization in the context of disease

Lactylation, a post-translational alteration facilitated by lactic acidderived lactyl-CoA, has emerged as an epigenetic regulator that alters gene expression in macrophages. Emerging data situates lactylation at the nexus of metabolic flux and immune cell destiny, especially in tumor and inflammatory microenvironments.

Lactylation is significantly linked to tumor progression and the polarization of macrophages towards the M2 phenotype, a condition that exacerbates cancer and associated inflammation. Modulating lactylation levels can alter the M1/M2 balance, hence affecting the progression of cancer and inflammatory illnesses. These findings identify lactylation as aregulator that can either suppress or enhance tumor development and the related inflammatory response, contingent upon the context and degree of the change.

This review systematically elucidates the role of lactylation in directing macrophage polarization in the context of cancer and associated inflammation. The aggregated data suggest that targeting lactylation constitutes an innovative therapeutic strategy for regulating immune cell activity and managing the advancement of cancer and related inflammatory conditions.

The conversion of lactate to lactyl-CoA facilitates enzymatic histone lactylation, transforming glycolytic byproducts into an epigenetic regulatory mechanism for gene expression. Lactylation modification influences macrophage polarization towards M1 or M2 phenotypes, affecting outcomes in infection, cancer, and fibrosis. Targeting lactylation modifiers through pharmacological means introduces a novel metabolic-epigenetic approach for treating disorders.