@article{8149ffc2ac444b11a5a7fe1aaad37725,
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.}",
note = "Funding Information: We thank D. Hume for providing MacBlue mice; T. Kaisho for providing XCR1-Venus mice; J. Cyster for providing us with Ccr2 −/− mice. We thank A. G{\'e}rard for initial work in developing explanted LN imaging. K. Corbin for early technical assistance. All members of the Krummel laboratory, BIDC, and A. Denton for discussion and support. Funding: This work was supported in part by Cancer Research Institute (United States) postdoctoral fellowships to M.K.R. and to E.W.R., NIH (United States) grant 5T32AI007334-28 to M.K.R., Human Frontier Science Program Fellowship LT000061/2018-L to N.K.S. and U54CA163123 , 5U01CA217864 , R21CA191428 , and R01CA197363 to M.F.K. We acknowledge the PFCC for assistance generating flow cytometry data. Research reported here was supported in part by the DRC Center grant NIH P30 DK063720 and by the NIH S10 Instrumentation grant S10 1S10OD018040-01 . Funding Information: We thank D. Hume for providing MacBlue mice; T. Kaisho for providing XCR1-Venus mice; J. Cyster for providing us with Ccr2?/? mice. We thank A. G?rard for initial work in developing explanted LN imaging. K. Corbin for early technical assistance. All members of the Krummel laboratory, BIDC, and A. Denton for discussion and support. Funding: This work was supported in part by Cancer Research Institute (United States) postdoctoral fellowships to M.K.R. and to E.W.R. NIH (United States) grant 5T32AI007334-28 to M.K.R. Human Frontier Science Program Fellowship LT000061/2018-L to N.K.S. and U54CA163123, 5U01CA217864, R21CA191428, and R01CA197363 to M.F.K. We acknowledge the PFCC for assistance generating flow cytometry data. Research reported here was supported in part by the DRC Center grant NIH P30 DK063720 and by the NIH S10 Instrumentation grant S10 1S10OD018040-01. M.K.R. and E.W.R designed and conducted most experiments, data analysis, and drafted the manuscript. E.C. performed LLS data analysis. A.M.M. performed the Ccr2?/? experiments and triple reporter flow cytometry. K.M. and C.B. assisted with LLS. D.N. generated the B16 CreERT2 loxp-mCherry-loxp-ZsGreen cell line. N.K.S. and M.B. discussed data and project direction. M.F.K. designed the experiments, interpreted the data, and with other authors, developed the manuscript. Authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = jun,
day = "8",
doi = "10.1016/j.ccell.2020.05.002",
language = "English (US)",
volume = "37",
pages = "786--799.e5",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}