AUTHOR=Yang Biao , Li Lingyu , Shi Dongmei , Zhong Tao , Xiong Huabao 

TITLE=Lactylation and antitumor immunity

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1690068

DOI=10.3389/fimmu.2025.1690068

ISSN=1664-3224

ABSTRACT=Lactylation, a recently discovered post-translational modification (PTM), plays a critical role in cancer biology. Warburg effect induces lactate accumulation, which serves as a metabolic end-product and intercellular signaling mediator within the tumor microenvironment (TME). Beyond fueling tumor growth, elevated lactate levels drive histone and non-histone lactylation, which modulates gene expression and protein function. This epigenetic reprogramming induces immunosuppressive phenotypes in immune cells that are resident in the tumor microenvironment, including impaired effector function, enhanced immunosuppressive cytokine secretion, and altered tumor antigen presentation, collectively facilitating immune escape. This review provides a synthesis of the current understanding of lactate and lactylation in tumor immunosuppression, detailing molecular mechanisms underlying immune cell inhibition (tumor-associated macrophages, T cells, T-reg cells, NK cells and NKT cells, as well as neutrophils) and evaluating emerging therapeutic strategies (e.g., inhibitors of MCTs/LDHA, site-specific antibodies, genetic code expansion technology). We aimed to accelerate the clinical translation of lactylation-targeted anticancer therapies by highlighting recent advances.