Gene transfer of human interferon gamma complementary DNA into a renal cell carcinoma line enhances MHC-restricted cytotoxic T lymphocyte recognition but suppresses non-MHC-restricted effector cell activity.
Even though renal cell carcinomas (RCC) are thought to be immunogenic, many tumors express variations in surface molecules and intracellular proteins that hinder induction of optimal antitumor responses. Interferon gamma (IFNgamma) stimulation can correct some of these deficiencies. Therefore, we introduced the complementary DNA (cDNA) encoding human IFNgamma into a well-characterized RCC line that has been selected for development of an allogeneic tumor cell vaccine for treatment of patients with metastatic disease. Studies were performed to determine how endogenous IFNgamma expression influences tumor cell immunogenicity. IFNgamma transductants showed minimal increases in surface expression of MHC class I and adhesion molecules but expression of class II molecules was induced. Proteins of the transporter associated with antigen processing (TAP) and low molecular weight polypeptide (LMP) were constitutively expressed at high levels. The transductants stimulated allospecific cytotoxic T lymphocytes (CTL); however, they were not better than unmodified tumor cells in this capacity. Endogenous IFNgamma expression enhanced tumor cell recognition by MHC-restricted, tumor antigen-specific CTL but suppressed recognition by non-MHC-restricted cytotoxic cells. Thus, the functional consequences of IFNgamma expression varied with respect to the type of effector cell and were not always beneficial for tumor cell recognition.
Schendel
D J
DJ
Institute of Molecular Immunology, GSF National Research Center for the Environment and Health, Munich, Germany.
Falk
C S
CS
Nössner
E
E
Maget
B
B
Kressenstein
S
S
Urlinger
S
S
Tampé
R
R
Gansbacher
B
B
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003546:Cysteine Endopeptidases; D018076:DNA, Complementary; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008163:Luminescent Measurements; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D009097:Multienzyme Complexes; D011506:Proteins; C073119:TAP1 protein, human; C071313:LMP-2 protein; C071692:TAP2 protein, human; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex