Lactate modulation of immune responses in inflammatory versus tumour microenvironments

Nat Rev Immunol. 2021 Mar;21(3):151-161. doi: 10.1038/s41577-020-0406-2. Epub 2020 Aug 24.

Abstract

The microenvironment in cancerous tissues is immunosuppressive and pro-tumorigenic, whereas the microenvironment of tissues affected by chronic inflammatory disease is pro-inflammatory and anti-resolution. Despite these opposing immunological states, the metabolic states in the tissue microenvironments of cancer and inflammatory diseases are similar: both are hypoxic, show elevated levels of lactate and other metabolic by-products and have low levels of nutrients. In this Review, we describe how the bioavailability of lactate differs in the microenvironments of tumours and inflammatory diseases compared with normal tissues, thus contributing to the establishment of specific immunological states in disease. A clear understanding of the metabolic signature of tumours and inflammatory diseases will enable therapeutic intervention aimed at resetting the bioavailability of metabolites and correcting the dysregulated immunological state, triggering beneficial cytotoxic, inflammatory responses in tumours and immunosuppressive responses in chronic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biological Availability
  • Carrier Proteins / metabolism
  • Humans
  • Inflammation / immunology*
  • L-Lactate Dehydrogenase / metabolism
  • Lactic Acid / metabolism*
  • Membrane Proteins / metabolism
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / metabolism
  • Tumor Microenvironment / immunology*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Thyroid Hormones
  • Lactic Acid
  • L-Lactate Dehydrogenase