Increased tumorigenicity, but unchanged immunogenicity, of transporter for antigen presentation 1-deficient tumors.
The lack of transporter-for-antigen-presentation (TAP)-1 expression by tumor cells prevents the processing and presentation of MHC class I-restricted tumor antigens. This could affect T-cell-dependent tumor immunity in either the priming or the effector phase. We have established TAP1(+) and TAP1(-) tumor cell lines using ras-transformed NIH3T3 fibroblasts. Impaired TAP1 expression by tumor cells increased their tumorigenicity in immunocompetent, but not in T-cell-deficient, mice. For the generation of tumor immunity, TAP1 expression was not necessary on tumor cells used for vaccination. However, in previously immunized mice TAP1(+) tumor cells were more efficiently rejected than were TAP1(-) tumor cells. CD8(+) T cells infiltrated both TAP1(+)- and TAP1(-)-challenge tumors and were required for tumor rejection. In mixed tumor/lymphocyte culture, TAP1 expression by tumor cells significantly increased the IFN-gamma production of antigen-specific spleen cells from immunized, but not from naive, mice. Thus, the lack of TAP1 expression did not change the immunogenicity of tumor cells. It may enable tumor cells to escape T-cell recognition during the effector phase of an antitumor immune response.
Qin
Zhihai
Z
Institute of Immunology, Universitaetsklinikum Benjamin Franklin, Haus IA, Hindenburgdamm 30, Free University of Berlin, 12200 Berlin, Germany. zhihai@ukbf.fu-berlin.de
Harders
Christina
C
Cao
Xuetao
X
Huber
Christoph
C
Blankenstein
Thomas
T
Seliger
Barbara
B
D016475:3T3 Cells; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002461:Cell Line, Transformed; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D007371:Interferon-gamma