Cancer Cell
Volume 37, Issue 6, 8 June 2020, Pages 786-799.e5
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Article
Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

https://doi.org/10.1016/j.ccell.2020.05.002Get rights and content
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Highlights

  • Myeloid cells retain tumor-derived antigens in intracellular vesicles

  • Dynamic synapses facilitate membrane and vesicular exchange between myeloid cells

  • Migratory DC pass vesicular tumor antigen to resident DC at points of contact

  • Migratory versus resident cDC1 exhibit differential T cell priming characteristics

Summary

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

dendritic cells
CD8+ T cells
tumor immunology
antigen trafficking
lymph node
T cell priming
antigen presentation

Cited by (0)

3

Present address: Beatson Institute for Cancer Research, Glasgow, UK

4

Present address: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

5

Present address: Pionyr Immunotherapeutics, San Francisco, CA 94107, USA

6

These authors contributed equally

7

Lead Contact