Enhanced stimulation of human tumor-specific T cells by dendritic cells matured in the presence of interferon-γ and multiple toll-like receptor agonists

• DOI: 10.1007/s00262-017-2029-4
• Publication Date: 2017-06-10T13:49:03Z
• 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
• Keywords: TLR3; TLR7

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 establish a protocol generate DC with greater immunostimulatory capacity. Immature were generated from healthy donor monocytes by culturing the presence of IL-4 and GM-CSF further differentiated into mature addition cocktails containing different cytokines toll-like receptor (TLR) agonists. Overall, IFNγ TLR7/8 agonist R848 during maturation was essential for production high levels IL-12p70 which augmented adding TLR3 poly I:C. In addition, matured IFNγ, R848, I:C also induced upregulation several other pro-inflammatory Th1-skewing cytokines/chemokines, co-stimulatory receptors, chemokine CCR7. For most chemokines even potentiated TLR4 LPS. Concurrently, anti-inflammatory cytokine IL-10 modest. Most importantly, had ability activate allogeneic T cells this enhanced LPS cocktail. Furthermore, epitope-specific stimulation TCR-transduced peptide- or whole tumor lysate-loaded efficiently stimulated only full cocktail three TLR ligands I:C, suggest that is used future trials anti-cancer vaccines.