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  • IMMUNITY  (2)
  • 1
    Keywords: CELLS ; tumor ; TUMOR-CELLS ; IN-VIVO ; TUMORS ; MICE ; RESPONSES ; CUTTING EDGE ; IFN-GAMMA ; ANTIGEN ; T-CELLS ; TOLERANCE ; bone marrow ; RECOGNITION ; LYMPHOCYTES ; IMMUNITY ; REJECTION ; CROSS-PRESENTATION ; EXOGENOUS ANTIGEN ; NONHEMATOPOIETIC CELLS ; PRESENTING CELLS
    Abstract: CD8(+) effector T cells recognize malignant cells by monitoring their surface for the presence of tumor-derived-peptides bound to MHC class I molecules. In addition, tumor-derived-Ags can be cross-presented to CD8(+) effector T cells by APCs. IFN-gamma production by CD8(+) T cells is often critical for tumor rejection. However, it remained unclear whether 1) CD8(+) T cells secrete IFN-gamma in response to Ag recognition on tumor cells or APCs and 2) whether IFN-gamma mediates its antitumor effect by acting on host or tumor cells. We show in this study that CD8(+) effector T cells can reject tumors in bone marrow- chimeric mice incapable of cross-presenting Ag by bone marrow- derived APCs and that tumor rejection required host cells to express IFN-gammaR. Together, CD8(+) effector T cells recognize Ag directly on tumor cells, and this recognition is sufficient to reject tumors by IFN-gamma acting on host cells
    Type of Publication: Journal article published
    PubMed ID: 12707316
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  • 2
    Keywords: CANCER ; CELLS ; GROWTH ; PROTECTION ; tumor ; carcinoma ; CELL ; MODEL ; TUMORS ; MICE ; PATIENT ; DNA ; IFN-GAMMA ; T cell ; T cells ; T-CELL ; T-CELLS ; BREAST ; breast cancer ; BREAST-CANCER ; cytokines ; antibodies ; antibody ; SWEDEN ; SURFACE ; VACCINE ; CANCER-PATIENTS ; CARCINOMAS ; CD8(+) ; immune response ; IMMUNE-RESPONSE ; IMMUNITY ; T-LYMPHOCYTES ; vaccination ; REJECTION ; CANCER PATIENTS ; CTL ; INTERFERON-GAMMA ; EFFECTOR ; GM-CSF ; HER-2/neu ; IMMUNIZATION ; ABSENCE ; CYTOKINE ; tumor immunity ; ANTI-ERBB-2 ANTIBODY ; anti-tumor immunity ; DNA vaccine ; ERBB-2 DNA ; PROTOONCOGENE
    Abstract: HER-2/neu (HER-2) is a cell surface proto-oncogene that is often overexpressed in carcinomas. Passive administration of anti-HER-2 antibodies in breast cancer patients has achieved promising results, but less is known about the role of antibodies in active immunization. We asked whether B cells/ antibodies are needed for tumor immunity induced by plasmid (HER-2 and GM-CSF) immunization. HER-2 specific tumor immunity relied completely on both CD4(+) and CD8(+) T cells. IFN-gamma, and to a lesser extent IL-4, seemed to be crucial cytokines during tumor rejection. Protection was associated with production of anti-HER-2 IgG antibodies in B cell competent mice. After immunization, however, B cell-deficient mice rejected HER-2-expressing tumors as efficiently as control littermates. We conclude that T cells are the main effector cells in DNA vaccine induced immunity against HER-2 and that anti HER-2 antibodies are not necessary to elicit a protective anti tumor immune response in this model. (C) 2003 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 14750178
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