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Blood, 1 January 2008, Vol. 111, No. 1, pp. 219-228. Prepublished online as a Blood First Edition Paper on September 20, 2007; DOI 10.1182/blood-2007-04-086835. This Article Full Text (PDF) All Versions of this Article: blood-2007-04-086835v1 111/1/219    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pan, P.-Y. Articles by Chen, S.-H. Search for Related Content PubMed PubMed Citation Articles by Pan, P.-Y. Articles by Chen, S.-H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 24, 2007 Accepted September 7, 2007 Reversion of immune tolerance in advanced malignancy: modulation of myeloid derived suppressor cell development by blockade of SCF function Ping-Ying Pan, George X Wang, Bingjiao Yin, Junko Ozao, Teresa Ku, Celia M Divino, and Shu-Hsia Chen* Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY, United States Department of General Surgery, Mount Sinai School of Medicine, New York, NY, United States * Corresponding author; email: shu-hsia.chen{at}mssm.edu. Tumor growth induced a significant increase of myeloid-derived suppressor cells (MDSC) in the tumor-bearing host. In our previous study, we showed that MDSC induced tumor-specific T-cell tolerance and the development of T regulatory cells (Treg). Tumor-derived factors have been implicated in the accumulation of MDSC. We hypothesize that reduction of MDSC accumulation in tumor-bearing hosts, through the blockade of tumor factors, can prevent T-cell anergy and Treg development and thereby improve immune therapy for the treatment of advanced tumors. Several tumor-derived factors were identified by gene array analysis. Among the candidate factors, stem cell factor (SCF) is expressed by various human and murine carcinomas and was selected for further study. Mice bearing tumor cells with SCF siRNA knockdown exhibited significantly reduced MDSC expansion and restored proliferate responses of tumor-infiltrating T cells. More importantly, blockade of SCF receptor (ckit)-SCF interaction by anti-c-kit prevented tumor-specific T cell anergy, Treg development, and tumor angiogenesis. Furthermore, the prevention of MDSC accumulation in conjunction with immune activation therapy showed synergistic therapeutic effect when treating mice bearing large tumors. This information supports the notion that modulation of MDSC development may be required to achieve effective immune-enhancing therapy for the treatment of advanced tumors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Ilkovitch and D. M. Lopez The Liver Is a Site for Tumor-Induced Myeloid-Derived Suppressor Cell Accumulation and Immunosuppression Cancer Res., July 1, 2009; 69(13): 5514 - 5521. [Abstract] [Full Text] [PDF] S. Mandruzzato, S. Solito, E. Falisi, S. Francescato, V. Chiarion-Sileni, S. Mocellin, A. Zanon, C. R. Rossi, D. Nitti, V. Bronte, et al. IL4R{alpha}+ Myeloid-Derived Suppressor Cell Expansion in Cancer Patients J. Immunol., May 15, 2009; 182(10): 6562 - 6568. [Abstract] [Full Text] [PDF] S. Ostrand-Rosenberg and P. Sinha Myeloid-Derived Suppressor Cells: Linking Inflammation and Cancer J. Immunol., April 15, 2009; 182(8): 4499 - 4506. [Abstract] [Full Text] [PDF] T. W. Poh, J. 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