Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

Cancer Cell. 2020 Jun 8;37(6):786-799.e5. doi: 10.1016/j.ccell.2020.05.002.

Abstract

Generation of tumor-infiltrating lymphocytes begins when tumor antigens reach the lymph node (LN) to stimulate T cells, yet we know little of how tumor material is disseminated among the large variety of antigen-presenting dendritic cell (DC) subsets in the LN. Here, we demonstrate that tumor proteins are carried to the LN within discrete vesicles inside DCs and are then transferred among DC subsets. A synapse is formed between interacting DCs and vesicle transfer takes place in the absence of free exosomes. DCs -containing vesicles can uniquely activate T cells, whereas DCs lacking them do not. Understanding this restricted sharing of tumor identity provides substantial room for engineering better anti-tumor immunity.

Keywords: CD8+ T cells; T cell priming; antigen presentation; antigen trafficking; dendritic cells; lymph node; tumor immunology.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Antigens, Neoplasm / immunology*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Male
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism
  • Receptors, CCR2 / physiology
  • Receptors, CCR7 / physiology
  • Synapses / immunology*
  • Synapses / metabolism
  • Synapses / pathology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, Neoplasm
  • Ccr2 protein, mouse
  • Ccr7 protein, mouse
  • Receptors, CCR2
  • Receptors, CCR7