Elevated circulating lactate in late-stage melanoma patients.

Area of Science:

• Oncology
• Cancer Metabolism
• Immunology

Background:

• Tumors exhibit high glucose consumption and lactate excretion (Warburg-like metabolism) to fuel rapid proliferation.
• Extracellular lactate, once considered a metabolic waste, is now recognized for its pro-tumorigenic roles, including promoting metastasis and immune evasion.
• Lactate can act as an alternative metabolic substrate and directly modify histones, influencing gene expression.

Purpose of the Study:

• To determine if late-stage cancer patients have increased circulating lactate levels.
• To investigate the correlation between elevated lactate and response to immunotherapy.
• To explore the relationship between circulating lactate, pyruvate, and immune cell determinants in melanoma patients.

Main Methods:

• Assayed plasma metabolites (lactate, pyruvate, glucose, LDH) in 38 stage III/IV melanoma patients and 10 healthy controls.
• Stratified patient data based on therapeutic responses, particularly to immunotherapy.
• Correlated metabolite levels with circulating immune cell profiles, including activated CD8+ T cells.

Main Results:

• Late-stage melanoma patients demonstrated significantly elevated circulating lactate levels compared to controls.
• Higher plasma lactate levels correlated with non-responsiveness to immune checkpoint blockade (ICB).
• Elevated circulating pyruvate was observed in melanoma patients, strongly correlating with lactate and predicting ICB non-responsiveness, alongside reduced activated CD8+ T cells.

Conclusions:

• Elevated circulating lactate in late-stage melanoma patients is linked to immune evasion mechanisms.
• Pyruvate may serve as a predictive biomarker for immunotherapy response in melanoma.
• Findings support previous research in mouse models connecting lactate to tumor-induced immune suppression.