Modulators of arginine metabolism support cancer immunosurveillance
Open Access
- 9 January 2009
- journal article
- Published by Springer Science and Business Media LLC in BMC Immunology
- Vol. 10 (1), 1
- https://doi.org/10.1186/1471-2172-10-1
Abstract
Tumor-associated accrual of myeloid derived suppressor cells (MDSC) in the blood, lymphoid organs and tumor tissues may lead to perturbation of the arginine metabolism and impairment of the endogenous antitumor immunity. The objective of this study was to evaluate whether accumulation of MDSC occurred in Th2 prone BALB/c and Th1 biased C57BL/6 mice bearing the C26GM colon carcinoma and RMA T lymphoma, respectively, and to investigate whether N(G) nitro-L-arginine methyl ester (L-NAME) and sildenafil, both modulators of the arginine metabolism, restored antitumor immunity. We report here that MDSC accumulate in the spleen and blood of mice irrespective of the mouse and tumor model used. Treatment of tumor-bearing mice with either the phosphodiesterase-5 inhibitor sildenafil or the nitric-oxide synthase (NOS) inhibitor L-NAME significantly restrained tumor growth and expanded the tumor-specific immune response. Our data emphasize the role of MDSC in modulating the endogenous tumor-specific immune response and underline the anti-neoplastic therapeutic potential of arginine metabolism modulators.This publication has 44 references indexed in Scilit:
- Pathways Mediating the Expansion and Immunosuppressive Activity of Myeloid-Derived Suppressor Cells and Their Relevance to Cancer TherapyClinical Cancer Research, 2007
- Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancerNature Medicine, 2007
- Altered macrophage differentiation and immune dysfunction in tumor developmentJCI Insight, 2007
- Tregs and rethinking cancer immunotherapyJCI Insight, 2007
- Immunosuppressive Strategies that are Mediated by Tumor CellsAnnual Review of Immunology, 2007
- The Terminology Issue for Myeloid-Derived Suppressor CellsCancer Research, 2007
- Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell functionThe Journal of Experimental Medicine, 2006
- Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cellsJCI Insight, 2006
- Monocyte and macrophage heterogeneityNature Reviews Immunology, 2005
- Regulation of immune responses by L-arginine metabolismNature Reviews Immunology, 2005