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Titolo:
INTRODUCTION OF THE INTERFERON-GAMMA GENE INTO MOUSE T-LYMPHOMA-CELLSWITH LOW MHC CLASS-I-EXPRESSION RESULTS IN SELECTIVE INDUCTION OF H-2D(K) AND CONCOMITANT ENHANCED METASTASIS
Autore:
GELDHOF AB; VANDENDRIESSCHE T; OPDENAKKER G; DEBAETSELIER P;
Indirizzi:
FREE UNIV BRUSSELS,FLEMISH INTERUNIV INST BIOTECHNOL,CELLULAR IMMUNOLLAB,BLDG IMOLII B-1640 RHODE ST GENESE BELGIUM CATHOLIC UNIV LEUVEN,REGA INST,IMMUNOBIOL LAB B-3000 LOUVAIN BELGIUM
Titolo Testata:
Cancer immunology and immunotherapy
fascicolo: 6, volume: 42, anno: 1996,
pagine: 329 - 338
SICI:
0340-7004(1996)42:6<329:IOTIGI>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
NATURAL-KILLER-CELLS; TUMOR-CELLS; IMMUNE INTERFERON; MELANOMA-CELLS; COMPLEX; ANTIGENS; MOLECULES; LYSIS; CDNA; IDENTIFICATION;
Keywords:
IFN-GAMMA; TRANSFECTION; NK CELLS; MHC CLASS I; METASTASIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
A.B. Geldhof et al., "INTRODUCTION OF THE INTERFERON-GAMMA GENE INTO MOUSE T-LYMPHOMA-CELLSWITH LOW MHC CLASS-I-EXPRESSION RESULTS IN SELECTIVE INDUCTION OF H-2D(K) AND CONCOMITANT ENHANCED METASTASIS", Cancer immunology and immunotherapy, 42(6), 1996, pp. 329-338

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 classI expression results in a selective induction of H-2D(k) but unaltered H-2K(k) expression. In earlier reports we demonstrated a positive correlation between H-2D(k) expression and enhanced metastatic potentialof BW variants. In accordance with these observations, we observed that intravenous inoculation of LiDlo(IFN gamma) variants into syngeneicAKR mice led to enhanced metastasis as compared to parental LiDlo andLiDlo(neo) control transfectants. Tumor cells, derived from local subcutaneous tumors or sporadic metastases from mice inoculated with LiDlo tumor cells, were found to upregulate H-2D(k) 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 that LiDlo and LiDlo(neo) tumor cells were NK-sensitive, while theBW 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-2D(k), (b) H-2D(k) governs susceptibility towards NK cells, and (c) NK susceptibility determines the experimental metastatic behavior of BW tumor cells.

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Documento generato il 15/08/20 alle ore 19:53:40