Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives

Immunol Rev. 2008 Apr;222:180-91. doi: 10.1111/j.1600-065X.2008.00608.x.

Abstract

Patients with cancer have an impaired T-cell response that can decrease the potential therapeutic benefit of cancer vaccines and other forms of immunotherapy. L-arginine (L-Arg) is a conditionally essential amino acid that is fundamental for the function of T lymphocytes. Recent findings in tumor-bearing mice and cancer patients indicate that increased metabolism of L-Arg by myeloid derived suppressor cells (MDSCs) producing arginase I inhibits T-lymphocyte responses. Here we discuss some of the most recent concepts how MDSC expressing arginase I may regulate T-cell function in cancer and other chronic inflammatory diseases and suggest possible therapeutic interventions to overcome this inhibitory effect.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Arginase / immunology
  • Arginase / metabolism
  • Arginine / immunology*
  • Arginine / metabolism
  • CD3 Complex / immunology
  • Enzyme Induction
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immune Tolerance*
  • Immunotherapy
  • Mice
  • Models, Immunological
  • Myeloid Cells / immunology*
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Escape*

Substances

  • CD3 Complex
  • CD3 antigen, zeta chain
  • Arginine
  • Arginase