Journal
SCIENCE ADVANCES
Volume 6, Issue 11, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaz1580
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Funding
- NIH [1R01CA026412, R01-AI097206, R01GM118486]
- NSF Graduate Research Fellowship Program
- Fahmy Lab
- Yale Cancer Center
- NY Cardiac Center [GS056321]
- NIAMSD Training Grant [5T32AR007016]
- Cancer Research Institute Irvington Postdoctoral Fellowship
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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 icB. 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.
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