Modulation of cancer-specific immune responses by amino acid degrading enzymes

Immunotherapy. 2017 Jan;9(1):83-97. doi: 10.2217/imt-2016-0118.

Abstract

To evade immune destruction, tumors exploit a wide range of immune escape mechanisms, including the induction of an immunosuppressive tumor microenvironment. This is mediated, in part, by amino acid degrading enzymes indoleamine 2,3-dioxygenase, tryptophan 2,3-dioxygenase, arginase 1 and arginase 2, which have emerged as key players in the regulation of tumor-induced immune tolerance. Here we describe how the expression of tryptophan- and arginine-degrading enzymes by tumor and tumor-infiltrating cells can hamper cancer-specific immune responses, and discuss how this knowledge is being exploited to develop new strategies for cancer immunotherapy.

Keywords: arginase; immunosuppression; indoleamine 2,3-dioxygenase; tryptophan 2,3-dioxygenase; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Arginase / metabolism*
  • Humans
  • Immunity
  • Immunotherapy / methods*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Tryptophan Oxygenase / metabolism*
  • Tumor Escape

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Tryptophan Oxygenase
  • Arginase