Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

Megan K. Ruhland; Edward W. Roberts; En Cai; Adriana M. Mujal; Kyle Marchuk; Casey Beppler; David Nam; Nina K. Serwas; Mikhail Binnewies; Matthew F. Krummel

doi:10.1016/j.ccell.2020.05.002

Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

Megan K. Ruhland, Edward W. Roberts, En Cai, Adriana M. Mujal, Kyle Marchuk, Casey Beppler, David Nam, Nina K. Serwas, Mikhail Binnewies, Matthew F. Krummel

Research output: Contribution to journal › Article › peer-review

123 Scopus citations

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.

Original language	English (US)
Pages (from-to)	786-799.e5
Journal	Cancer Cell
Volume	37
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2020.05.002
State	Published - Jun 8 2020
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2020.05.002

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title = "Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells",

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",

author = "Ruhland, {Megan K.} and Roberts, {Edward W.} and En Cai and Mujal, {Adriana M.} and Kyle Marchuk and Casey Beppler and David Nam and Serwas, {Nina K.} and Mikhail Binnewies and Krummel, {Matthew F.}",

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doi = "10.1016/j.ccell.2020.05.002",

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T1 - Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

AU - Ruhland, Megan K.

AU - Roberts, Edward W.

AU - Cai, En

AU - Mujal, Adriana M.

AU - Marchuk, Kyle

AU - Beppler, Casey

AU - Nam, David

AU - Serwas, Nina K.

AU - Binnewies, Mikhail

AU - Krummel, Matthew F.

PY - 2020/6/8

Y1 - 2020/6/8

N2 - 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.

AB - 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.

KW - CD8+ T cells

KW - T cell priming

KW - antigen presentation

KW - antigen trafficking

KW - dendritic cells

KW - lymph node

KW - tumor immunology

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JO - Cancer Cell

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ER -

Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

Abstract

Keywords

ASJC Scopus subject areas

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