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BMC Immunology

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Open Access 01-12-2009 | Research article

Modulators of arginine metabolism support cancer immunosurveillance

Authors: Giusy Capuano, Nicolò Rigamonti, Matteo Grioni, Massimo Freschi, Matteo Bellone

Published in: BMC Immunology | Issue 1/2009

Abstract

Background

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.

Results

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.

Conclusion

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.

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Title: Modulators of arginine metabolism support cancer immunosurveillance
Authors: Giusy Capuano
Nicolò Rigamonti
Matteo Grioni
Massimo Freschi
Matteo Bellone
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: BMC Immunology / Issue 1/2009
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/1471-2172-10-1

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