| Type-1 polarized dendritic cells loaded with apoptotic prostate cancer cells are potent inducers of CD8(+) T cells against prostate cancer cells and defined prostate cancer-specific epitopes. | |
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MedLine Citation:
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PMID: 20717900 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: In order to develop improved vaccines for patients with recurrent prostate cancer (PCa), we tested the feasibility of using type-1 polarized dendritic cells (αDC1s) to cross-present antigens from allogeneic PCa cells and to induce functional CD8(+) T cell responses against PCa cells and against defined MHC class I-restricted PCa-relevant epitopes. METHODS: Monocyte-derived DCs from PCa patients were matured using the "standard" cytokine cocktail (IL-1β/TNFα/IL-6/PGE₂) or using the αDC1-polarizing cocktail (IL-1β/TNFα/IFNα/IFNγ/poly-I:C), loaded with UV-irradiated LNCaP cells, and used to sensitize autologous CD8(+) T cells. RESULTS: αDC1s from PCa patients secreted 10-30 times higher levels of IL-12p70 than sDCs. Importantly this elevated capacity for IL-12p70 secretion was not inhibited by loading with apoptotic tumor cells. Compared to standard DCs, αDC1s induced higher numbers of CD8(+) T cells capable of recognizing both the original PCa cells as well as another PCa cell line, DU145, in MHC class I-restricted fashion. Furthermore, αDC1s induced higher numbers of CD8(+) T cells recognizing defined PCa-specific class I-restricted peptide epitopes of prostate-specific antigen and prostatic acid phosphatase: PAP(135-143) (average 49-fold higher), PAP(112-120) (average 24-fold), PSA(141-150) (average 5.5-fold), and PSA(146-154) (average 11-fold). CONCLUSION: Type-1 polarization of GM-CSF/IL-4-generated DCs enhances their ability to present allogeneic tumor cells and to induce CD8(+) T cells recognizing different PCa cells and multiple defined PCa-specific epitopes. These observations help to develop improved immunotherapies of PCa for patients with different HLA types and lacking autologous tumor material. |
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Authors:
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Eva Wieckowski; Gurkamal S Chatta; Robbie M Mailliard; William Gooding; Karolina Palucka; Jacques Banchereau; Pawel Kalinski |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-17 |
Journal Detail:
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Title: The Prostate Volume: 71 ISSN: 1097-0045 ISO Abbreviation: Prostate Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2010-12-24 Completed Date: 2011-01-24 Revised Date: 2013-05-28 |
Medline Journal Info:
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Nlm Unique ID: 8101368 Medline TA: Prostate Country: United States |
Other Details:
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Languages: eng Pagination: 125-33 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
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Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alkaline Phosphatase
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analysis CD8-Positive T-Lymphocytes / immunology* Cancer Vaccines / immunology, therapeutic use* Cell Line, Tumor Dendritic Cells / immunology* Epitopes, T-Lymphocyte / immunology* Flow Cytometry Humans Immunotherapy, Adoptive / methods* Interleukin-12 / biosynthesis, immunology Male Prostate-Specific Antigen / analysis Prostatic Neoplasms / blood, immunology*, therapy* Th1 Cells / immunology |
| Grant Support | |
ID/Acronym/Agency:
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CA095128/CA/NCI NIH HHS; CA101944/CA/NCI NIH HHS; CA10373005/CA/NCI NIH HHS; CA114931/CA/NCI NIH HHS; P01 CA101944/CA/NCI NIH HHS; P01 CA101944-030002/CA/NCI NIH HHS; P01 CA101944-040002/CA/NCI NIH HHS; P01 CA101944-050002/CA/NCI NIH HHS; P20 CA103730-05/CA/NCI NIH HHS; R01 CA095128/CA/NCI NIH HHS; R01 CA095128-03/CA/NCI NIH HHS; R01 CA095128-04/CA/NCI NIH HHS; R01 CA095128-05A1/CA/NCI NIH HHS; R21 CA114931/CA/NCI NIH HHS; R21 CA114931-01/CA/NCI NIH HHS; R21 CA114931-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cancer Vaccines; 0/Epitopes, T-Lymphocyte; 187348-17-0/Interleukin-12; EC 3.1.3.1/Alkaline Phosphatase; EC 3.4.21.77/Prostate-Specific Antigen |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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