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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Schadler, KL; Crosby, EJ; Zhou, AY; Bhang, DH; Braunstein, L; Baek, KH; Crawford, D; Crawford, A; Angelosanto, J; Wherry, EJ; Ryeom, S

Published Date

  • April 15, 2014

Published In

Volume / Issue

  • 74 / 8

Start / End Page

  • 2171 - 2181

PubMed ID

  • 24590059

Pubmed Central ID

  • PMC4061618

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-13-0094

Language

  • eng

Conference Location

  • United States