Modulators of arginine metabolism support cancer immunosurveillance

Autor: Freschi Massimo, Grioni Matteo, Rigamonti Nicolò, Capuano Giusy, Bellone Matteo
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: BMC Immunology, Vol 10, Iss 1, p 1 (2009)
Druh dokumentu: article
ISSN: 1471-2172
DOI: 10.1186/1471-2172-10-1
Popis: 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.
Databáze: Directory of Open Access Journals