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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 (författare)
- Karolinska Institutet,Uppsala universitet,Klinisk immunologi,Karolinska Institute; Karolinska University Hospital
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- Sarhan, Dhifaf (författare)
- Karolinska Institutet
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- Truxova, Iva (författare)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Choudhary, Bhavesh (författare)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Maas, Roeltje (författare)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Melief, Jeroen (författare)
- Karolinska Institutet
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- Nystrom, Maria (författare)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Edback, Ulrika (författare)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Vermeij, Renee (författare)
- Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
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- Scurti, Gina (författare)
- Loyola Univ Chicago, Dept Surg, Maywood, IL USA.
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- Nishimura, Michael (författare)
- Loyola Univ Chicago, Dept Surg, Maywood, IL USA.
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- Masucci, Giuseppe (författare)
- Karolinska Institutet
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- Karlsson-Parra, Alex (författare)
- Uppsala universitet,Klinisk immunologi
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- Lundqvist, Andreas (författare)
- Karolinska Institutet
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- Adamson, Lars (författare)
- Karolinska Institutet
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- Kiessling, Rolf (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-06-10
- 2017
- Engelska.
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Ingår i: Cancer Immunology and Immunotherapy. - : SPRINGER. - 0340-7004 .- 1432-0851. ; 66:10, s. 1333-1344
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://link.springe...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Cancer
- Dendritic cell-vaccine
- IFN gamma
- R848
- Poly I:C
- LPS
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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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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visa fler...
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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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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Cancer Immunolog ...
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet