Lactate and lactylation in tumor immunity

Area of Science:

• Cancer Metabolism
• Immunology
• Tumor Microenvironment (TME)

Background:

• The Warburg effect describes tumor cell metabolic reprogramming to glycolysis, leading to rapid energy production.
• This metabolic shift results in lactate accumulation, creating an acidic tumor microenvironment (TME).
• The acidic TME impairs immune cell function and promotes tumor progression.

Purpose of the Study:

• To comprehensively review lactate's role as an immunosuppressive molecule within the TME.
• To elucidate the mechanisms by which lactate modulates immune cell function.
• To highlight lactate's importance in immune regulation within the TME for novel therapeutic insights.

Main Methods:

• Literature review focusing on lactate's impact on immune cells in the TME.
• Examination of molecular mechanisms including membrane receptor binding and lactate shuttle transport.
• Analysis of epigenetic regulation via histone and nonhistone lactylation.

Main Results:

• Lactate acts as a key immunosuppressive signaling molecule in the TME.
• Lactate influences immune cell function through various mechanisms, including receptor binding and transport.
• Epigenetic modifications, such as lactylation, are involved in lactate-mediated immune suppression.

Conclusions:

• Lactate plays a critical role in immune suppression within the tumor microenvironment.
• Understanding lactate's immunosuppressive functions provides a basis for developing targeted therapies.
• Targeting lactate offers novel insights for developing effective immunosuppressive cancer treatments.