The immune regulation in cancer by the amino acid metabolizing enzymes ARG and IDO

Curr Opin Pharmacol. 2017 Aug;35:30-39. doi: 10.1016/j.coph.2017.05.002. Epub 2017 May 26.

Abstract

Some enzymes degrading amino acids have evolved in mammals to dampen immune responses and maintain peripheral tolerance. The enzymes metabolizing l-arginine and l-tryptophan are particularly powerful, contributing to restrain immunity towards fetal tissues and establish neonatal tolerance. Solid tumors can hijack these formidable pathways to construct a microenvironment highly unfavorable to anti-tumor T lymphocytes able to recognize them, one of mechanisms for their immune evasion. In this review, we analyze emerging concepts in the cross-talk between cells expressing these enzymes, their immune regulatory functions and pharmacological approaches that can target them to enhance cancer immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Arginase / immunology*
  • Dendritic Cells / immunology
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology*
  • Neoplasms / immunology*
  • Transforming Growth Factor beta / immunology
  • Tryptophan / immunology
  • Tryptophan / metabolism
  • Tumor Microenvironment / immunology

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Transforming Growth Factor beta
  • Tryptophan
  • Arginase