PT  - JOURNAL ARTICLE
AU  - Han, Patrick
AU  - Hanlon, Douglas
AU  - Arshad, Najla
AU  - Lee, Jung Seok
AU  - Tatsuno, Kazuki
AU  - Robinson, Eve
AU  - Filler, Renata
AU  - Sobolev, Olga
AU  - Cote, Christine
AU  - Rivera-Molina, Felix
AU  - Toomre, Derek
AU  - Fahmy, Tarek
AU  - Edelson, Richard
TI  - Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes
AID  - 10.1126/sciadv.aaz1580
DP  - 2020 Mar 01
TA  - Science Advances
PG  - eaaz1580
VI  - 6
IP  - 11
4099  - http://advances.sciencemag.org/content/6/11/eaaz1580.short
4100  - http://advances.sciencemag.org/content/6/11/eaaz1580.full
SO  - Sci Adv2020 Mar 01; 6
AB  - 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.