A gamma-herpesvirus immune evasion gene allows tumor cells in vivo to escape attack by cytotoxic T cells specific for a tumor epitope.
DNA vaccines induce CTL attack on target tumor epitopes, but tumor elimination in vivo also requires sufficient effector CTL to enter the site, guided by inflammatory chemokines. Many herpesviruses contain genes for chemokine and chemokine receptor-like proteins to protect infected cells from immune attack. To assess if this evasion strategy could protect tumor cells, we used a model where CTL specific for a single epitope were the only effectors. Following DNA vaccination, CTL eliminated tumor cells from a subcutaneous site. However, introducing a viral gene encoding a secreted broad-spectrum chemokine-binding protein (M3) into tumor cells completely blocked CTL attack. Transduced tumor cells also protected neighboring non-transduced tumor. These findings confirm the importance of chemokines for migration of CTL to a non-lymphoid site. They may have relevance for escape of human virus-associated malignancies, and raise the question of whether analogous molecules might contribute to the failure of CTL to eliminate tumors.
Rice
Jason
J
Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Southampton, GB.
de Lima
Brigitte
B
Stevenson
Freda K
FK
Stevenson
Philip G
PG
D000818:Animals; D000951:Antigens, Neoplasm; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D018142:Gammaherpesvirinae / Q000235:genetics* / Q000276:immunology*; D005814:Genes, Viral; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; D000939:Epitopes; D019444:Vaccines, DNA; D014764:Viral Proteins