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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2003-01-0190. This Article Full Text (PDF) All Versions of this Article: 2003-01-0190v1 102/6/2138    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 Melani, C. Articles by Colombo, M. P Search for Related Content PubMed PubMed Citation Articles by Melani, C. Articles by Colombo, M. P Social Bookmarking                   What's this? Submitted January 22, 2003 Accepted May 7, 2003 Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity Cecilia Melani*, Claudia Chiodoni, Guido Forni, and Mario P Colombo Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy * Corresponding author; email: melani{at}istitutotumori.mi.it. Transgenic female mice expressing the transforming rat oncogene c-erbB-2 (HER-2/neu) under the MMTV promoter (BALB-neuT) spontaneously develop mammary carcinomas with a progression resembling that of human breast cancer. In these mice activating anti-tumor immunotherapy fails to induce T cell-mediated cytotoxicity, suggesting a suppression of the immune response. We found a direct correlation between tumor multiplicity and an increased proportion of Gr-1/Mac-1/ER-MP12-positive immature myeloid cells in the peripheral blood (PB) and spleen, suggesting that tumor load profoundly affects overall BALB-neuT hemopoiesis. In fact, myeloid colony formation was increased in bone marrow (BM) and spleen. The immature myeloid cells displayed suppressive activity on host T lymphocytes, which progressively failed to respond to allo-antigens and CD3 triggering, while maintaining the ability to proliferate in response to non-specific mitogens. Transplantation of normal BM into BALB-neuT mice readily resulted in hypertrophic hemopoiesis with myeloid cell expansion. This persistent influence of the tumor was mediated through the release of VEGF but not GM-CSF, and was down-modulated when tumor load was reduced but not when BM was transplanted. Together, the data obtained in the BALB-neuT model of naturally occurring carcinogenesis show that tumor-associated immune suppression is secondary to a more general alteration of host hemopoiesis, conditioned by tumor-secreted soluble factors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. C. McKenna, K. M. Beatty, R. A. Bilonick, L. Schoenfield, K. L. Lathrop, and A. D. Singh Activated CD11b+ CD15+ Granulocytes Increase in the Blood of Patients with Uveal Melanoma Invest. Ophthalmol. Vis. Sci., September 1, 2009; 50(9): 4295 - 4303. [Abstract] [Full Text] [PDF] 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] T. J. Stewart, D. J. Liewehr, S. M. Steinberg, K. M. Greeneltch, and S. I. 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