Title: Introduction of the interferon gamma gene into mouse T lymphoma cells with low MHC class I-expression results in selective induction of H-2Dk and concomitant enhanced metastasis
Authors: Geldhof, A B ×
Vandendriessche, Thierry
Opdenakker, Ghislain
De Baetselier, P #
Issue Date: Nov-1996
Series Title: Cancer immunology, immunotherapy : CII vol:42 issue:6 pages:329-38
Abstract: Interferon-gamma (IFN gamma)-induced up-regulation of MHC class I expression on tumor cells can induce a potent CD8-mediated antitumor response. Consequently, many investigators have proposed IFN gamma gene transfection as a means to immunogenize tumor cells and to vaccinate against metastatic disease. In this study, we demonstrate that transfection of the IFN gamma gene in a BW5147 variant (LiDlo) with low MHC class I expression results in a selective induction of H-2Dk but unaltered H-2Kk expression. In earlier reports we demonstrated a positive correlation between H-2Dk expression and enhanced metastatic potential of BW variants. In accordance with these observations, we observed that intravenous inoculation of LiDlo(IFN gamma) variants into syngeneic AKR mice led to enhanced metastasis as compared to parental LiDlo and LiDlo(neo) control transfectants. Tumor cells, derived from local subcutaneous tumors or sporadic metastases from mice inoculated with LiDlo tumor cells, were found to up-regulate H-2Dk selectively. Anti-asialoGM1 treatment of AKR mice allowed rapid experimental metastasis formation by the LiDlo and LiDlo(neo) variants, indicating that natural killer (NK) cells control the metastatic behavior of these tumor cells. This was corroborated by in vitro cytotoxicity experiments, demonstrating the LiDlo and LiDlo(neo) tumor cells were NK-sensitive, while the BW IFN gamma transfectants became resistant to lymphokine-activated killer cells and poly(I).poly(C)-induced NK cells. We thus conclude that (a) IFN gamma up-regulates selectively the MHC class I antigen H-2Dk, (b) H-2Dk governs susceptibility towards NK cells, and (c) NK susceptibility determines the experimental metastatic behavior of BW tumor cells.
ISSN: 0340-7004
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Laboratory of Immunobiology (Rega Institute)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science