Arginase, Nitric Oxide Synthase, and Novel Inhibitors of L-Arginine Metabolism in Immune Modulation

Susanna Mandruzzato, Simone Mocellin, Vincenzo Bronte

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

This chapter provides a brief introduction about nitric oxide synthase (NOS) and arginase (ARG). It discusses the immunoregulatory activities of ARG and NOS. Tumor growth is associated with an altered metabolism of the amino acid L-arginine (L-Arg) by the enzymes nitric oxide synthase (NOS) and arginase (ARG). Once activated, either in tumor-recruited myeloid cells or the cancerous cells, both enzymes can alter the function of the antitumor T lymphocytes. The prevalence of one enzyme pathway or cooperation between both pathways depends on the tumor type and the genetic background of the host. Experimental findings indicate that when, either one of the two enzymes is active, the net effect on T lymphocytes can be attributed to the cell cycle arrest, whereas the concomitant activation of both the enzymes in the same environment can lead to T cell death by apoptosis. Moreover, immune regulation by L-Arg metabolism is not antigen specific but requires the activation of T cells through their clonotypic T cell receptor in order to be susceptible to these inhibitory circuits.

Original languageEnglish
Title of host publicationCancer Immunotherapy
PublisherElsevier Inc.
Pages369-399
Number of pages31
ISBN (Print)9780123725516
DOIs
Publication statusPublished - 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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