Lysine Lactylation: Dynamic Regulation in the Tumor Microenvironment and Clinical Translational Prospects

Area of Science:

• Biochemistry
• Immunology
• Oncology

Background:

• Lysine lactylation (Kla) is an emerging post-translational modification.
• Kla is linked to the Warburg effect and lactate production in tumors.
• Kla influences tumor metabolism and immune cell function within the tumor microenvironment (TME).

Purpose of the Study:

• To review the regulatory roles of Kla in the TME.
• To explore the clinical translational potential of Kla.
• To understand Kla's impact on tumor metabolism and immune evasion.

Main Methods:

• Systematic review of existing literature.
• Analysis of Kla's mechanistic roles in key signaling pathways (HIF-1α, mTOR, NF-κB).
• Evaluation of preclinical studies targeting lactate metabolism and lactylation enzymes.

Main Results:

• Kla reprograms tumor metabolism and reshapes immune landscapes.
• Kla promotes immunosuppressive cells and inhibits cytotoxic T cells and NK cells, aiding immune escape.
• Targeting lactate metabolism or lactylation enzymes can restore immune function and improve immunotherapy efficacy.

Conclusions:

• Kla plays a dynamic regulatory role in the TME, impacting tumor progression and immune evasion.
• Targeting Kla presents a potential strategy for cancer therapy, particularly in combination with immune checkpoint inhibitors.
• Further research is needed to address challenges like tumor heterogeneity and to explore Kla's potential as a biomarker and therapeutic target.