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A gamma-herpesvirus immune evasion gene allows tumor cells in vivo to escape attack by cytotoxic T cells specific for a tumor epitope

A gamma-herpesvirus immune evasion gene allows tumor cells in vivo to escape attack by cytotoxic T cells specific for a tumor epitope
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 herpes viruses 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.
chemokine, tumor immunity, vaccination, chemotaxis
0014-2980
3481-3487
Rice, Jason
d58d4fcd-8dc0-4599-bf96-62323d579227
de Lima, Brigitte
19b8a2b8-ac39-4d85-867d-a0833544aaa9
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Stevenson, Philip G.
e0954faa-afe3-4288-b738-38095a925106
Rice, Jason
d58d4fcd-8dc0-4599-bf96-62323d579227
de Lima, Brigitte
19b8a2b8-ac39-4d85-867d-a0833544aaa9
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Stevenson, Philip G.
e0954faa-afe3-4288-b738-38095a925106

Rice, Jason, de Lima, Brigitte, Stevenson, Freda K. and Stevenson, Philip G. (2002) A gamma-herpesvirus immune evasion gene allows tumor cells in vivo to escape attack by cytotoxic T cells specific for a tumor epitope. European Journal of Immunology, 32 (12), 3481-3487. (doi:10.1002/1521-4141(200212)32:12<3481::AID-IMMU3481>3.0.CO;2-J).

Record type: Article

Abstract

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 herpes viruses 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.

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More information

Published date: 2002
Keywords: chemokine, tumor immunity, vaccination, chemotaxis

Identifiers

Local EPrints ID: 26569
URI: http://eprints.soton.ac.uk/id/eprint/26569
ISSN: 0014-2980
PURE UUID: 83a821f2-1f70-4796-9a13-6fe035db0e68
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

Catalogue record

Date deposited: 20 Apr 2006
Last modified: 16 Mar 2024 02:54

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Contributors

Author: Jason Rice
Author: Brigitte de Lima
Author: Philip G. Stevenson

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