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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-07-1956. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-1956v1 101/12/4878    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 Ohm, J. E. Articles by Carbone, D. P. Search for Related Content PubMed PubMed Citation Articles by Ohm, J. E. Articles by Carbone, D. P. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Immunobiology Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2003, Vol. 101, No. 12, pp. 4878-4886 IMMUNOBIOLOGY VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression Joyce E. Ohm, Dmitry I. Gabrilovich, Gregory D. Sempowski, Ekaterina Kisseleva, Kelly S. Parman, Sorena Nadaf, and David P. Carbone From the Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN; the H. Lee Moffitt Cancer Center at the University of South Florida, Tampa, FL; the Department of Medicine, Human Vaccine Institute, Duke University Medical Center, Durham, NC; the Institute of Experimental Medicine, St Petersburg, Russia; and the Mouse Pathology & Immunohistochemistry Core, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN. T-cell defects and premature thymic atrophy occur in cancer patients and tumor-bearing animals. We demonstrate that exposure of mice to recombinant vascular endothelial growth factor (VEGF) at concentrations similar to those observed in advanced stage cancer patients reproduces this profound thymic atrophy and is highlighted by a dramatic reduction in CD4+/CD8+ thymocytes. We find that VEGF does not induce thymocyte apoptosis, but instead rapidly decreases the number of the earliest observable progenitors in the thymus. VEGF does not inhibit thymocyte development in fetal thymic organ culture, further suggesting a prethymic effect. We also demonstrate that bone marrow progenitors from animals infused with recombinant VEGF and transferred to irradiated untreated animals recolonize the thymus more efficiently than progenitors from control animals. This suggests that VEGF exposure is associated with an increased population of thymus-committed progenitors in the bone marrow. We hypothesize that pathophysiologically relevant concentrations of VEGF may block the differentiation and/or emigration of these progenitors resulting in the observed thymic atrophy. Removal of VEGF via cessation of infusion or adoptive transfer of progenitors to a congenic host induces a preferential commitment of lymphoid progenitors to the T lineage and results in a restoration of the normal composition and cellularity of the thymus. These data demonstrate that at pathophysiologic concentrations, VEGF interferes with the development of T cells from early hematopoetic progenitor cells and this may contribute to tumor-associated immune deficiencies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. B. Dorff, A. Goldkorn, and D. I. Quinn Review: Targeted therapy in renal cancer Therapeutic Advances in Medical Oncology, November 1, 2009; 1(3): 183 - 205. [Abstract] [PDF] M. Sabatino, S. Kim-Schulze, M. C. Panelli, D. Stroncek, E. Wang, B. Taback, D. W. Kim, G. DeRaffele, Z. Pos, F. M. Marincola, et al. Serum Vascular Endothelial Growth Factor and Fibronectin Predict Clinical Response to High-Dose Interleukin-2 Therapy J. Clin. Oncol., June 1, 2009; 27(16): 2645 - 2652. [Abstract] [Full Text] [PDF] M. E. HANDEL-FERNANDEZ, D. ILKOVITCH, V. IRAGAVARAPU-CHARYULU, L. M. HERBERT, and D. M. 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