Targeting ectonucleotidases to treat inflammation and halt cancer development in the gut

Biochem Pharmacol. 2021 May:187:114417. doi: 10.1016/j.bcp.2021.114417. Epub 2021 Jan 15.

Abstract

CD39 and CD73 control cell immunity by hydrolyzing proinflammatory ATP and ADP (CD39) into AMP, subsequently converted into anti-inflammatory adenosine (CD73). By regulating the balance between effector and regulatory cells, these ectonucleotidases promote immune homeostasis in acute and chronic inflammation; while also appearing to limit antitumor effector immunity in gut cancer. This manuscript focuses on the pivotal role of CD39 and CD73 ectonucleotidase function in shaping immune responses in the gut. We focus on those mechanisms deployed by these critical and pivotal ectoenzymes and the regulation in the setting of gastrointestinal tract infections, inflammatory bowel disease and tumors of the gastrointestinal tract. We will highlight translational and clinical implications of the latest and most innovative basic research discoveries of these important players of the purinergic signaling. Immunotherapeutic strategies that have been developed to either boost or control ectonucleotidase expression and activity in important disease settings are also reviewed and the in vivo effects discussed.

Keywords: CD39; CD73; Effector lymphocytes; Gastrointestinal inflammation; Regulatory T-cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • 5'-Nucleotidase / antagonists & inhibitors
  • 5'-Nucleotidase / metabolism*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Apyrase / antagonists & inhibitors
  • Apyrase / metabolism
  • Drug Delivery Systems / methods*
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / metabolism*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism*
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • GPI-Linked Proteins
  • Gastrointestinal Agents
  • 5'-Nucleotidase
  • NT5E protein, human
  • Apyrase
  • ENTPD1 protein, human