Histone lactylation regulates cancer progression by reshaping the tumor microenvironment

Front Immunol. 2023 Oct 27:14:1284344. doi: 10.3389/fimmu.2023.1284344. eCollection 2023.

Abstract

As a major product of glycolysis and a vital signaling molecule, many studies have reported the key role of lactate in tumor progression and cell fate determination. Lactylation is a newly discovered post-translational modification induced by lactate. On the one hand, lactylation introduced a new era of lactate metabolism in the tumor microenvironment (TME), and on the other hand, it provided a key breakthrough point for elucidation of the interaction between tumor metabolic reprogramming and epigenetic modification. Studies have shown that the lactylation of tumor cells, tumor stem cells and tumor-infiltrating immune cells in TME can participate in the development of cancer through downstream transcriptional regulation, and is a potential and promising tumor treatment target. This review summarized the discovery and effects of lactylation, as well as recent research on histone lactylation regulating cancer progression through reshaping TME. We also focused on new strategies to enhance anti-tumor effects via targeting lactylation. Finally, we discussed the limitations of existing studies and proposed new perspectives for future research in order to further explore lactylation targets. It may provide a new way and direction to improve tumor prognosis.

Keywords: cancer therapy; epigenetic modification; immune cells; lactylation; tumor microenvironment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Histones*
  • Humans
  • Lactic Acid
  • Neoplasms*
  • Tumor Microenvironment

Substances

  • Histones
  • Lactic Acid

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is supported by grants from National Natural Science Foundation youth fund of China (32200714); Henan Normal University Research Launch Foundation (20220099) to ZS; Xinxiang Medical University Research Launch Foundation (505501) to JQ.