Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Apr:222:180-91.
doi: 10.1111/j.1600-065X.2008.00608.x.

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

Paulo C Rodríguez  1 , Augusto C Ochoa
Affiliations
Review

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

Paulo C Rodríguez et al. Immunol Rev. 2008 Apr.

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1. l-Arg metabolism
l-Arginine can be metabolized by NOS into NO and citrulline. Alternatively, arginase (I and II) can convert l-Arg into urea and ornithine, with the latter being the substrate for the synthesis of polyamines need to sustain cell proliferation. For the sake of simplicity, emphasis is on enzymes that directly metabolize l-Arg. This diagram should not be interpreted to indicate that all of these enzymes are expressed simultaneously in any given cell type.
Fig. 2
Fig. 2. Control of translation by eIF2α
Multiple signals can trigger the phosphorylation of eIF2α, including nutrient starvation (GCN2), dsRNA (PKN), unfolded proteins (PERK), and oxidative stress (HRI). Phospho-eIF2α binds to the IF2β complex, preventing its translocation and inhibiting translation.
Fig. 3
Fig. 3. T-cell dysfunction induced by arginase I
Tumor cells expressing COX-2 and releasing PGE2 induce the expression of arginase I and CAT-2B in MDSC. This expression leads to a reduction of extracellular levels of l-Arg, which activates GCN2 and inhibits the expression of CD3ζ, cyclin D3, and cdk4 through post-transcriptional and translational mechanisms.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Miescher S, Whiteside TL, Carrel S, von FV. Functional properties of tumor-infiltrating and blood lymphocytes in patients with solid tumors: effects of tumor cells and their supernatants on proliferative responses of lymphocytes. J Immunol. 1986;136:1899–1907. - PubMed
    1. Miescher S, Stoeck M, Qiao L, Barras C, Barrelet L, von Fliedner V. Preferential clonogenic deficit of CD8-positive T-lymphocytes infiltrating human solid tumors. Cancer Res. 1988;48:6992–6998. - PubMed
    1. Whiteside TL, Miescher S, Moretta L, von Fliedner V. Cloning and proliferating precursor frequencies of tumor-infiltrating lymphocytes from human solid tumors. Transplant Proc. 1988;20:342–343. - PubMed
    1. Whiteside TL, Rabinowich H. The role of Fas/FasL in immunosuppression induced by human tumors. Cancer Immunol Immunother. 1998;46:175–184. - PMC - PubMed
    1. Hellstrom I, Sjogren HO, Warner G, Hellstrom KE. Blocking of cell-mediated tumor immunity by sera from patients with growing neoplasms. Int J Cancer. 1971;7:226–237. - PubMed

Publication types

MeSH terms