The Tumor Metabolic Microenvironment: Lessons from Lactate.

TitleThe Tumor Metabolic Microenvironment: Lessons from Lactate.
Publication TypeJournal Article
Year of Publication2019
AuthorsGarcía-Cañaveras, JC, Chen, L, Rabinowitz, JD
JournalCancer Res
Volume79
Issue13
Pagination3155-3162
Date Published2019 Jul 01
ISSN1538-7445
Abstract

The extracellular milieu of tumors is generally assumed to be immunosuppressive due in part to metabolic factors. Here, we review methods for probing the tumor metabolic microenvironment. In parallel, we consider the resulting available evidence, with a focus on lactate, which is the most strongly increased metabolite in bulk tumors. Limited microenvironment concentration measurements suggest depletion of glucose and modest accumulation of lactate (less than 2-fold). Isotope tracer measurements show rapid lactate exchange between the tumor and circulation. Such exchange is catalyzed by MCT transporters, which cotransport lactate and protons (H+). Rapid lactate exchange seems at odds with tumor lactate accumulation. We propose a potential resolution to this paradox. Because of the high pH of tumor cells relative to the microenvironment, H+-coupled transport by MCTs tends to drive lactate from the interstitium into tumor cells. Accordingly, lactate may accumulate preferentially in tumor cells, not the microenvironment. Thus, although they are likely subject to other immunosuppressive metabolic factors, tumor immune cells may not experience a high lactate environment. The lack of clarity regarding microenvironmental lactate highlights the general need for careful metabolite measurements in the tumor extracellular milieu.

DOI10.1158/0008-5472.CAN-18-3726
Alternate JournalCancer Res.
PubMed ID31171526
PubMed Central IDPMC6606343
Grant ListP30 CA072720 / CA / NCI NIH HHS / United States
R01 CA163591 / CA / NCI NIH HHS / United States