Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes

Sci Adv. 2020 Mar 11;6(11):eaaz1580. doi: 10.1126/sciadv.aaz1580. eCollection 2020 Mar.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Blood Platelets / immunology*
  • Calcium Signaling / genetics
  • Calcium Signaling / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Dendritic Cells / immunology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Transgenic
  • Monocytes / immunology*
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • P-Selectin / genetics
  • P-Selectin / immunology*
  • T-Lymphocytes / immunology


  • Antigens, Neoplasm
  • Membrane Glycoproteins
  • NF-kappa B
  • P-Selectin
  • P-selectin ligand protein