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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 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Immunobiology Transplantation Oncogenes and Tumor Suppressors Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2138-2145 IMMUNOBIOLOGY 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 From the Immunotherapy and Gene Therapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy, and the Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy. Transgenic female mice expressing the transforming rat oncogene c-erbB-2 (HER-2/neu) under the mouse mammary tumor virus (MMTV) promoter (BALB-neuT) spontaneously develop mammary carcinomas with a progression resembling that of human breast cancer. In these mice, activating antitumor 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+ (Ly6G)/Mac-1+(CD11b)/ER-MP12+(CD31) immature myeloid cells in the peripheral blood (PB) and spleen, suggesting that tumor load profoundly affects overall BALB-neuT hematopoiesis. 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 alloantigens and CD3 triggering, while maintaining the ability to proliferate in response to nonspecific mitogens. Transplantation of normal BM into BALB-neuT mice readily resulted in hypertrophic hematopoiesis with myeloid cell expansion. This persistent influence of the tumor was mediated through the release of vascular endothelial growth factor (VEGF) but not granulocyte-macrophage colony-stimulating factor (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 hematopoiesis, 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. 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Forni, P. Musiani, W.-Z. Wei, and F. Cavallo Immunosurveillance of erbb2 carcinogenesis in transgenic mice is concealed by a dominant regulatory T-cell self-tolerance. Cancer Res., August 1, 2006; 66(15): 7734 - 7740. [Abstract] [Full Text] [PDF] J. A. Van Ginderachter, S. Meerschaut, Y. Liu, L. Brys, K. De Groeve, G. Hassanzadeh Ghassabeh, G. Raes, and P. De Baetselier Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer Blood, July 15, 2006; 108(2): 525 - 535. [Abstract] [Full Text] [PDF] R. Yang, Z. Cai, Y. Zhang, W. H. Yutzy IV, K. F. Roby, and R. B.S. Roden CD80 in Immune Suppression by Mouse Ovarian Carcinoma-Associated Gr-1+CD11b+ Myeloid Cells. Cancer Res., July 1, 2006; 66(13): 6807 - 6815. [Abstract] [Full Text] [PDF] X. Song, Y. Krelin, T. Dvorkin, O. Bjorkdahl, S. Segal, C. A. Dinarello, E. Voronov, and R. N. 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Owens Neutrophils That Infiltrate the Central Nervous System Regulate T Cell Responses J. Immunol., April 15, 2005; 174(8): 5124 - 5131. [Abstract] [Full Text] [PDF] C. De Santo, P. Serafini, I. Marigo, L. Dolcetti, M. Bolla, P. Del Soldato, C. Melani, C. Guiducci, M. P. Colombo, M. Iezzi, et al. Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination PNAS, March 15, 2005; 102(11): 4185 - 4190. [Abstract] [Full Text] [PDF] P. Serafini, R. Carbley, K. A. Noonan, G. Tan, V. Bronte, and I. Borrello High-Dose Granulocyte-Macrophage Colony-Stimulating Factor-Producing Vaccines Impair the Immune Response through the Recruitment of Myeloid Suppressor Cells Cancer Res., September 1, 2004; 64(17): 6337 - 6343. [Abstract] [Full Text] [PDF] A. M. Dring, F. E. Davies, J. A. L. Fenton, P. L. Roddam, K. Scott, D. Gonzalez, S. Rollinson, A. C. Rawstron, K. S. Rees-Unwin, C. Li, et al. A Global Expression-based Analysis of the Consequences of the t(4;14) Translocation in Myeloma Clin. Cancer Res., September 1, 2004; 10(17): 5692 - 5701. [Abstract] [Full Text] [PDF]

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