Abstract:
:Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen-specific immunity. Clinically, however, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited success. We hypothesized that DCs produced in a physiological manner may be more effective and found that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18 hours) maturation into physiological DCs (phDCs). Differentiation of monocytes into phDCs was concomitant with the formation of an "adhesion synapse," a biophysical junction enriched with platelet P-selectin and monocyte P-selectin glycoprotein ligand 1, followed by intracellular calcium fluxing and nuclear localization of nuclear factor κB. phDCs were more efficient than cytokine-derived DCs in generating tumor-specific T cell immunity. Our findings demonstrate that platelets mediate a cytokine-independent, physiologic maturation of DC and suggest a novel strategy for DC-based immunotherapies.
journal_name
Sci Advjournal_title
Science advancesauthors
Han P,Hanlon D,Arshad N,Lee JS,Tatsuno K,Robinson E,Filler R,Sobolev O,Cote C,Rivera-Molina F,Toomre D,Fahmy T,Edelson Rdoi
10.1126/sciadv.aaz1580subject
Has Abstractpub_date
2020-03-11 00:00:00pages
eaaz1580issue
11issn
2375-2548pii
aaz1580journal_volume
6pub_type
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