Lactate Metabolism in the Metastatic Cascade: Microenvironmental Remodeling, Epigenetic Reprogramming, and...

Area of Science:

• Oncology
• Metabolic Signaling
• Cancer Metastasis

Background:

• Lactate is increasingly recognized beyond its role as a metabolic byproduct.
• It functions as a key signaling molecule in cancer progression and metastasis.

Purpose of the Study:

• To comprehensively review how tumor-derived lactate remodels the tumor microenvironment (TME).
• To elucidate lactate's role in facilitating cancer cell dissemination and immune evasion.
• To explore therapeutic strategies targeting lactate metabolism.

Main Methods:

• Review of existing literature on lactate metabolism in cancer.
• Analysis of lactate's role in spatial compartmentalization, extracellular acidification, and epigenetic modulation.
• Examination of lactate's impact on immune cells within the TME.

Main Results:

• Lactate, via MCTs, fuels invasive cancer cell subpopulations and promotes extracellular acidification, driving epithelial-mesenchymal transition (EMT).
• Intracellular lactate epigenetically regulates gene expression and suppresses anti-tumor immunity via lactylation.
• Lactate impairs CD8+ T cell function and promotes immunosuppressive cells (Tregs, M2 macrophages).

Conclusions:

• Targeting lactate metabolism presents therapeutic potential, but monotherapies face resistance.
• Network pharmacology of Traditional Chinese Medicine offers multi-targeted approaches.
• Integrated therapies combining metabolic interventions with immune checkpoint blockade show promise for preventing metastasis and relapse.