title: Immunosurveillance by antiangiogenesis: tumor growth arrest by T cell-derived thrombospondin-1.
abstract: 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.
authors.affiliation: Authors' Affiliations: Department of Cancer Biology, Abramson Family Cancer Research Institute; Department of Microbiology, Institute for Immunology, Perelman School of Medicine; Department of Pathobiology, Veterinary School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Children's Hospital, Boston, Massachusetts; and Department of Molecular and Cellular Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Keri L
authors.initials: KL
authors.lastname: Schadler
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Crosby
authors.forename: Alice Yao
authors.initials: AY
authors.lastname: Zhou
authors.forename: Dong Ha
authors.initials: DH
authors.lastname: Bhang
authors.forename: Lior
authors.initials: L
authors.lastname: Braunstein
authors.forename: Kwan Hyuck
authors.initials: KH
authors.lastname: Baek
authors.forename: Danielle
authors.initials: D
authors.lastname: Crawford
authors.forename: Alison
authors.initials: A
authors.lastname: Crawford
authors.forename: Jill
authors.initials: J
authors.lastname: Angelosanto
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Sandra
authors.initials: S
authors.lastname: Ryeom
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000276:immunology; D018929:Cell Culture Techniques; D007157:Immunologic Surveillance; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D019700:Thrombospondin 1