REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1690068
This article is part of the Research TopicMetabolism in the Tumour Microenvironment: Implications for Pathogenesis and TherapeuticsView all 7 articles
Lactylation and Antitumor Immunity
Provisionally accepted- 1Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China
- 2Jining No 1 People's Hospital, Jining, China
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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.
Keywords: lactylation, antitumor immunity, lactate accumulation, Tumor Microenvironment, histone and non-histone lactylation, immunosuppressive phenotypes
Received: 21 Aug 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Xiong, Yang, Li, Shi and Zhong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Huabao Xiong, xionghbl@yahoo.com
Dongmei Shi, shidongmei28@163.com
Tao Zhong, zhongtao@mail.jnmc.edu.cn
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