Title |
Enhanced stimulation of human tumor-specific T cells by dendritic cells matured in the presence of interferon-γ and multiple toll-like receptor agonists
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Published in |
Cancer Immunology, Immunotherapy, June 2017
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DOI | 10.1007/s00262-017-2029-4 |
Pubmed ID | |
Authors |
Tanja Lövgren, Dhifaf Sarhan, Iva Truxová, Bhavesh Choudhary, Roeltje Maas, Jeroen Melief, Maria Nyström, Ulrika Edbäck, Renee Vermeij, Gina Scurti, Michael Nishimura, Giuseppe Masucci, Alex Karlsson-Parra, Andreas Lundqvist, Lars Adamson, Rolf Kiessling |
Abstract |
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 IFNγ 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 IFNγ, 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 IFNγ, R848, and poly I:C had the ability to activate IFNγ 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 IFNγ 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 54 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 11 | 20% |
Student > Ph. D. Student | 9 | 17% |
Student > Master | 7 | 13% |
Student > Doctoral Student | 3 | 6% |
Professor > Associate Professor | 3 | 6% |
Other | 10 | 19% |
Unknown | 11 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 10 | 19% |
Immunology and Microbiology | 9 | 17% |
Biochemistry, Genetics and Molecular Biology | 8 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 9% |
Medicine and Dentistry | 5 | 9% |
Other | 5 | 9% |
Unknown | 12 | 22% |