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Enhanced stimulatio...
Enhanced stimulation of human tumor-specific T cells by dendritic cells matured in the presence of interferon-gamma and multiple toll-like receptor agonists
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- Lövgren, Tanja (author)
- Karolinska Institutet,Uppsala universitet,Klinisk immunologi,Karolinska Institute; Karolinska University Hospital
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- Sarhan, Dhifaf (author)
- Karolinska Institutet
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- Truxova, Iva (author)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Choudhary, Bhavesh (author)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Maas, Roeltje (author)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Melief, Jeroen (author)
- Karolinska Institutet
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- Nystrom, Maria (author)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Edback, Ulrika (author)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Vermeij, Renee (author)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Scurti, Gina (author)
- Loyola Univ Chicago, Dept Surg, Maywood, IL USA.
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- Nishimura, Michael (author)
- Loyola Univ Chicago, Dept Surg, Maywood, IL USA.
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- Masucci, Giuseppe (author)
- Karolinska Institutet
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- Karlsson-Parra, Alex (author)
- Uppsala universitet,Klinisk immunologi
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- Lundqvist, Andreas (author)
- Karolinska Institutet
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- Adamson, Lars (author)
- Karolinska Institutet
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- Kiessling, Rolf (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-06-10
- 2017
- English.
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In: Cancer Immunology and Immunotherapy. - : SPRINGER. - 0340-7004 .- 1432-0851. ; 66:10, s. 1333-1344
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Abstract
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- Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Immature DC were generated from healthy donor monocytes by culturing in the presence of IL-4 and GM-CSF and were further differentiated into mature DC by the addition of cocktails containing different cytokines and toll-like receptor (TLR) agonists. Overall, addition of IFN gamma and the TLR7/8 agonist R848 during maturation was essential for the production of high levels of IL-12p70 which was further augmented by adding the TLR3 agonist poly I:C. In addition, the DC matured with IFN gamma, R848, and poly I:C also induced upregulation of several other pro-inflammatory and Th1-skewing cytokines/chemokines, co-stimulatory receptors, and the chemokine receptor CCR7. For most cytokines and chemokines the production was even further potentiated by addition of the TLR4 agonist LPS. Concurrently, upregulation of the anti-inflammatory cytokine IL-10 was modest. Most importantly, DC matured with IFN gamma, R848, and poly I:C had the ability to activate IFN gamma production in allogeneic T cells and this was further enhanced by adding LPS to the cocktail. Furthermore, epitope-specific stimulation of TCR-transduced T cells by peptide- or whole tumor lysate-loaded DC was efficiently stimulated only by DC matured in the full maturation cocktail containing IFN gamma and the three TLR ligands R848, poly I:C, and LPS. We suggest that this cocktail is used for future clinical trials of anti-cancer DC vaccines.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Cancer
- Dendritic cell-vaccine
- IFN gamma
- R848
- Poly I:C
- LPS
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lövgren, Tanja
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Sarhan, Dhifaf
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Truxova, Iva
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Choudhary, Bhave ...
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Maas, Roeltje
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Melief, Jeroen
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show more...
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Nystrom, Maria
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Edback, Ulrika
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Vermeij, Renee
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Scurti, Gina
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Nishimura, Micha ...
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Masucci, Giusepp ...
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Karlsson-Parra, ...
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Lundqvist, Andre ...
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Adamson, Lars
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Kiessling, Rolf
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Immunolog ...
- By the university
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Uppsala University
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Karolinska Institutet