IL-4-Transfected Tumor Cell Vaccines Activate Tumor-Infiltrating Dendritic Cells and Promote Type-1 Immunity
| العنوان: | IL-4-Transfected Tumor Cell Vaccines Activate Tumor-Infiltrating Dendritic Cells and Promote Type-1 Immunity |
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| المؤلفون: | Junichi Eguchi, Fumihiko Nishimura, Manabu Hatano, Walter J. Storkus, Hideho Okada, Jill E. Dusak, Naruo Kuwashima |
| المصدر: | Scopus-Elsevier |
| بيانات النشر: | The American Association of Immunologists, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Graft Rejection, Adoptive cell transfer, Fibrosarcoma, medicine.medical_treatment, Immunology, Mice, Nude, Biology, Transfection, Cancer Vaccines, Interferon-gamma, Mice, Paracrine signalling, Cell Movement, T-Lymphocyte Subsets, Immunity, Cell Line, Tumor, Glioma, medicine, Animals, Immunology and Allergy, Interleukin 4, Mice, Knockout, Immunity, Cellular, Mice, Inbred BALB C, Interleukin-12 Subunit p40, Dendritic Cells, STAT4 Transcription Factor, medicine.disease, Interleukin-12, DNA-Binding Proteins, Killer Cells, Natural, Mice, Inbred C57BL, Protein Subunits, CTL, Cytokine, Cell culture, Trans-Activators, Female, Interleukin-4, Sarcoma, Experimental, STAT6 Transcription Factor |
| الوصف: | We previously demonstrated that IL-4 gene-transfected glioma cell vaccines induce effective therapeutic immunity in preclinical glioma models, and have initiated phase I trials of these vaccines in patients with malignant gliomas. To gain additional mechanistic insight into the efficacy of this approach, we have treated mice bearing the MCA205 (H-2b) or CMS-4 (H-2d) sarcomas. IL-12/23 p40−/− and IFN-γ−/− mice, which were able to reject the initial inoculation of IL-4 expressing tumors, failed to mount a sustained systemic response against parental (nontransfected) tumor cells. Paracrine production of IL-4 in vaccine sites promoted the accumulation and maturation of IL-12p70-secreting tumor-infiltrating dendritic cells (TIDCs). Adoptive transfer of TIDCs isolated from vaccinated wild-type, but not IL-12/23 p40−/−, mice were capable of promoting tumor-specific CTL responses in syngeneic recipient animals. Interestingly, both STAT4−/− and STAT6−/− mice failed to reject IL-4-transfected tumors in concert with the reduced capacity of TIDCs to produce IL-12p70 and to promote specific antitumor CTL reactivity. These results suggest that vaccines consisting of tumor cells engineered to produce the type 2 cytokine, IL-4, critically depend on type 1 immunity for their observed therapeutic efficacy. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::344ae0e9b5530111c42e4177469201deTest https://doi.org/10.4049/jimmunol.174.11.7194Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....344ae0e9b5530111c42e4177469201de |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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