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Review
. 2024 Oct;28(20):e70146.
doi: 10.1111/jcmm.70146.

A rising star involved in tumour immunity: Lactylation

Xu Zhang  1   2 , Changming Liang  1   2 , Chengwei Wu  1   2 , Senlin Wan  1   2 , Lishuai Xu  1   2 , Song Wang  1   2 , Jiawei Wang  1   2 , Xiaoxu Huang  1   2 , Li Xu  1   2
Affiliations
Review

A rising star involved in tumour immunity: Lactylation

Xu Zhang et al. J Cell Mol Med. 2024 Oct.

Abstract

In recent years, continuous exploration worldwide has revealed that some metabolites produced during cellular and tissue metabolism can act as signalling molecules to exert different effects on the human body. These metabolites may act as cofactors for proteases or as post-translational modifications linked to proteins. Lactate, a traditional metabolite, is found at high levels in the tumour microenvironment (TME). Many studies have shown that lactate influences tumorigenesis and development via different mechanisms, not only through the metabolic reprogramming of tumours but also through its significant impact on tumour immunity. Previously, tumour cells were reported to use glucose and glutamine to fuel lactate metabolism; however, lactate serves not only as an energy source for tumour cells but also as a precursor substance needed for the post-translational modification of proteins. Recent studies identified a novel form of epigenetic modification, lactate-mediated histone lysine lactylation (Kla) and demonstrated that histone lactylation directly stimulates chromatin after gene transcription; consequently, lactylation has become a popular research topic in recent years. This article focuses on the research progress and application prospects of lactylation in the context of tumour immunity.

Keywords: immunosuppression; lactate; lactylation; tumour.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
MCT1 transfers L‐lactate into the cell. The glycolysis byproduct pyruvate undergoes LDHA‐mediated conversion to produce L‐lactate. L‐lactate undergoes unknown enzymatic actions to synthesize lactyl‐CoA, which is involved in histone and nonhistone Kl‐la by the action of related writers. In addition, L‐lactate and ATP form lactate‐AMP and PPi in response to AARS1/2. Lactate‐AMP is covalently linked to lysines on target proteins. GLO1 conjugates MGO, a byproduct of glycolysis, to glutathione to form LGSH, which is then hydrolysed by GLO2 to produce D‐lactate and regenerate cellular glutathione. D‐la is formed by a noncatalytic reaction between LGSH and lysine residues of proteins. Kce is formed by a non‐catalytic reaction between MGO and lysine residues of proteins.
FIGURE 2
FIGURE 2
The lactylation is involved in tissue repair and induces fibroblasts to synthesize collagen, thus promoting skin rejuvenation. Lactylation is also involved in a variety of disease and tumour development processes.
FIGURE 3
FIGURE 3
Lactylation is involved in the formation of the TIME and regulates immune cells.
FIGURE 4
FIGURE 4
Inhibitors that target lactylation upstream and lactylation sites can be used in combination therapy for tumour immunity. Lactylation model constructs can be used to study tumour‐related mechanisms, guide therapy and early diagnosis.
See this image and copyright information in PMC

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