The Tumor Metabolic Microenvironment: Lessons from Lactate.

Area of Science:

• Oncology
• Cancer Metabolism
• Immunology

Background:

• Tumor extracellular milieu is often considered immunosuppressive due to metabolic factors.
• Lactate is a key metabolite with increased levels in bulk tumors.

Purpose of the Study:

• To review methods for probing the tumor metabolic microenvironment.
• To evaluate evidence on lactate accumulation and its impact on tumor immunity.

Main Methods:

• Review of existing literature on tumor metabolic microenvironment.
• Analysis of metabolite concentration measurements and isotope tracer studies.
• Examination of monocarboxylate transporter (MCT) function.

Main Results:

• Limited measurements show modest lactate accumulation (less than 2-fold) in the tumor microenvironment.
• Isotope tracer studies reveal rapid lactate exchange between tumors and circulation via MCTs.
• A proposed model suggests lactate accumulation within tumor cells, not the extracellular milieu, due to pH gradients.

Conclusions:

• Tumor immune cells might not be exposed to a high lactate environment.
• The paradox of rapid lactate exchange versus accumulation is resolved by intracellular sequestration.
• Accurate measurement of extracellular lactate is crucial for understanding tumor immunity.