Blood DCs activated with R848 and poly(I:C) induce antigen-specific immune responses against viral and tumor-associated antigens.
Blood dendritic cells
Conventional dendritic cells
Immunotherapy
Plasmacytoid dendritic cells
Toll-like receptors
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
received:
29
06
2021
accepted:
09
11
2021
pubmed:
26
11
2021
medline:
15
6
2022
entrez:
25
11
2021
Statut:
ppublish
Résumé
Monocyte-derived Dendritic cells (DCs) have successfully been employed to induce immune responses against tumor-associated antigens in patients with various cancer entities. However, objective clinical responses have only been achieved in a minority of patients. Additionally, generation of GMP-compliant DCs requires time- and labor-intensive cell differentiation. In contrast, Blood DCs (BDCs) require only minimal ex vivo handling, as differentiation occurs in vivo resulting in potentially better functional capacities and survival. We aimed to identify a protocol for optimal in vitro activation of BDCs including the three subsets pDCs, cDC1s, and cDC2s. We evaluated several TLR ligand combinations and demonstrated that polyinosinic:polycytidylic acid [poly(I:C)] and R848, ligands for TLR3 and TLR7/8, respectively, constituted the optimal combination for inducing a positive co-stimulatory profile in all BDC subsets. In addition, TLR3 and TLR7/8 activation led to high secretion of IFN-α and IL-12p70. Simultaneous as opposed to separate tailored activation of pDCs and cDCs increased immunostimulatory capacities, suggesting that BDC subsets engage in synergistic cross-talk during activation. Stimulation of BDCs with this protocol resulted in enhanced migration, high NK-cell activation, and potent antigen-specific T-cell induction.We conclude that simultaneous activation of all BDC subsets with a combination of R848 + poly(I:C) generates highly immunostimulatory DCs. These results support further investigation and clinical testing, as standalone or in conjunction with other immunotherapeutic strategies including adoptive T-cell transfer and checkpoint inhibition.
Identifiants
pubmed: 34821951
doi: 10.1007/s00262-021-03109-w
pii: 10.1007/s00262-021-03109-w
pmc: PMC8614222
doi:
Substances chimiques
Antigens, Neoplasm
0
Antigens, Viral
0
Toll-Like Receptor 3
0
Toll-Like Receptor 7
0
Toll-Like Receptor 8
0
Poly I-C
O84C90HH2L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1705-1718Subventions
Organisme : deutsche forschungsgemeinschaft
ID : SFB1243
Organisme : deutsche forschungsgemeinschaft
ID : SU197/3-1
Organisme : wilhelm sander-stiftung
ID : 2018.087.1
Informations de copyright
© 2021. The Author(s).
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