Premium
Role of Endothelial Cells in a Novel Mechanism of Tumor‐Induced Immune Suppression
Author(s) -
Mulligan Jennifer,
Young M. Rita I.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1078.7
Subject(s) - lewis lung carcinoma , endothelial stem cell , head and neck squamous cell carcinoma , cancer research , angiogenesis , immune system , biology , in vivo , immunology , chemistry , microbiology and biotechnology , medicine , in vitro , cancer , metastasis , biochemistry , head and neck cancer
Previous studies by our lab have shown that Lewis lung carcinoma (LLC)‐secreted products skew endothelial cells to suppress T cell, NK cell and macrophage functions. LLC‐derived VEGF has been identified as inducing endothelial cells to suppress T‐cell functions. In our current studies, we examined the role of endothelial cells in mediating suppression in human head and neck squamous cell carcinoma (HNSCC) and in the in vivo LLC tumor model. Antibody neutralization of HNSCC‐derived VEGF blocked tumor induced increases in endothelial cells production of VEGF and PGE 2 . T cells treated with HNSCC‐exposed endothelial cell conditioned media had decreased IFN‐γ production, compared to control treated T cells. Treatment of HNSCC‐conditioned media with VEGF neutralizing antibody prevented induction of suppressive endothelial cells toward T cell functions. We also examined the ability of tumors to induce suppressive endothelial cells in vivo . Conditioned media from endothelial cells isolated from the lungs of tumor‐bearing mice suppressed IFN‐γ production by CD8 + T cells and IL‐2 by CD4 + T cells as compared to normal lung controls. Studies are ongoing to determine the role of VEGF in the induction of suppressive endothelial cells in vivo. Together these studies implicate induction of suppressive endothelial cells as a novel mechanism of tumor‐induced immune suppression. Supported by Dept of Veterans Affairs & NIH