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Publication : Immunosurveillance by antiangiogenesis: tumor growth arrest by T cell-derived thrombospondin-1.

First Author  Schadler KL Year  2014
Journal  Cancer Res Volume  74
Issue  8 Pages  2171-81
PubMed ID  24590059 Mgi Jnum  J:210523
Mgi Id  MGI:5571405 Doi  10.1158/0008-5472.CAN-13-0094
Citation  Schadler KL, et al. (2014) Immunosurveillance by antiangiogenesis: tumor growth arrest by T cell-derived thrombospondin-1. Cancer Res 74(8):2171-81
abstractText  Recent advances in cancer immunotherapy suggest that manipulation of the immune system to enhance the antitumor response may be a highly effective treatment modality. One understudied aspect of immunosurveillance is antiangiogenic surveillance, the regulation of tumor angiogenesis by the immune system, independent of tumor cell lysis. CD4(+) T cells can negatively regulate angiogenesis by secreting antiangiogenic factors such as thrombospondin-1 (TSP-1). In tumor-bearing mice, we show that a Th1-directed viral infection that triggers upregulation of TSP-1 in CD4(+) and CD8(+) T cells can inhibit tumor angiogenesis and suppress tumor growth. Using bone marrow chimeras and adoptive T-cell transfers, we demonstrated that TSP-1 expression in the T-cell compartment was necessary and sufficient to inhibit tumor growth by suppressing tumor angiogenesis after the viral infection. Our results establish that tumorigenesis can be stanched by antiangiogenic surveillance triggered by an acute viral infection, suggesting novel immunologic approaches to achieve antiangiogenic therapy.
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