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Visualizing Synaptic Transfer of Tumor Antigens Amongst Dendritic Cells

53 Pages Posted: 9 Oct 2019 Publication Status: Review Complete

See all articles by Edward W. Roberts

Edward W. Roberts

University of California, San Francisco (UCSF) - Department of Pathology

Megan K. Ruhland

University of California, San Francisco (UCSF) - Department of Pathology

En Cai

University of California, San Francisco (UCSF) - Department of Pathology

Adriana M. Mujal

University of California, San Francisco (UCSF) - Department of Pathology

Kyle Marchuk

University of California, San Francisco (UCSF) - UCSF CoLabs

Casey Beppler

University of California, San Francisco (UCSF) - Department of Pathology

David Nam

University of California, San Francisco (UCSF) - Department of Pathology

Nina K. Serwas

University of California, San Francisco (UCSF) - Department of Pathology

Mikhail Binnewies

University of California, San Francisco (UCSF) - Department of Pathology

Matthew F. Krummel

University of California, San Francisco (UCSF) - Department of Pathology; University of California, San Francisco (UCSF) - Department of Anatomy

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Abstract

Tumors frequently program CD8 T cell immunity that is ‘exhausted’, or otherwise fails to provide for tumor clearance. This begins when tumor antigens reach the lymph node (LN) to stimulate T cells yet we know little of how tumor material is transported and disseminated amongst the large variety of antigen-presenting dendritic cell (DC) subsets in the LN.  Here, in vitro and in vivo assays together with lattice light sheet and multiphoton imaging we demonstrate that tumor proteins are carried to LN within discrete vesicles inside DC and are then transferred amongst DC subsets. A cup-on-cup synapse is formed between interacting DC and directed vesicle transfer takes place routinely in the absence of free exosomes. DC containing these vesicles can uniquely activate T cells whereas DC 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

Suggested Citation

Roberts, Edward W. and Ruhland, Megan K. and Cai, En and Mujal, Adriana M. and Marchuk, Kyle and Beppler, Casey and Nam, David and Serwas, Nina K. and Binnewies, Mikhail and Krummel, Matthew F., Visualizing Synaptic Transfer of Tumor Antigens Amongst Dendritic Cells (October 4, 2019). Available at SSRN: https://ssrn.com/abstract=3464654 or http://dx.doi.org/10.2139/ssrn.3464654
This version of the paper has not been formally peer reviewed.

Edward W. Roberts

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

Megan K. Ruhland

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

En Cai

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

Adriana M. Mujal

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

Kyle Marchuk

University of California, San Francisco (UCSF) - UCSF CoLabs ( email )

San Francisco, CA
United States

Casey Beppler

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

David Nam

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

Nina K. Serwas

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

Mikhail Binnewies

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

Matthew F. Krummel (Contact Author)

University of California, San Francisco (UCSF) - Department of Pathology ( email )

San Francisco, CA 94143
United States

University of California, San Francisco (UCSF) - Department of Anatomy ( email )

San Francisco, CA 94143
United States

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