Lactylation and tumor immune regulation: insights from recent studies

TL;DR

Lactylation, a new type of protein modification, influences tumor immune responses and could lead to new cancer treatments.

Contribution

This paper reviews recent findings on lactylation's role in tumor immunity and its potential as a therapeutic target.

Findings

Lactylation affects macrophage polarization and immune cell function in the tumor microenvironment.

Lactylation influences anti-tumor immunity and response to immunotherapy.

Targeting lactate metabolism and lactylation may improve cancer treatment outcomes.

Abstract

Lactate, a major product of glycolysis, accumulates abundantly in the tumor microenvironment (TME), serving not only as a hallmark of metabolic dysregulation but also as a key driver of immunosuppression. In recent years, lysine lactylation (Kla), a novel post-translational modification (PTM), has been identified, linking lactate metabolism closely with epigenetic regulation. Current studies indicate that lactylation modulates gene transcription and metabolic pathways in tumor cells while broadly influencing immune cell functions. For example, histone lactylation in macrophages promotes M2 polarization, enhancing immunosuppressive phenotypes; T cells, natural killer (NK) cells, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) may also be regulated by lactylation, thereby affecting anti-tumor immune responses and the efficacy of immune checkpoint inhibitors. As the mechanistic understanding of lactylation deepens, its roles in tumor immune evasion and therapy resistance are becoming increasingly evident. Targeting lactate metabolism and lactylation-related enzymatic processes, potentially in combination with immunotherapy, may represent a promising therapeutic strategy. This mini-review summarizes recent advances in lactylation research in tumor immunity and discusses its potential clinical implications and future directions.

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