Open AccessMetabolic labeling and targeted modulation of dendritic cells
Author(s) -
Hua Wang,
Miguel C. Sobral,
David Zhang,
Adam N.R. Cartwright,
Aileen Weiwei Li,
Maxence O. Dellacherie,
Christina M. Tringides,
Sandeep T. Koshy,
Kai W. Wucherpfennig,
David J. Mooney
Publication year - 2020
Publication title -
nature materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 14.344
H-Index - 483
eISSN - 1476-4660
pISSN - 1476-1122
DOI - 10.1038/s41563-020-0680-1
Subject(s) - priming (agriculture) , in vivo , dendritic cell , antigen , immune system , microbiology and biotechnology , t cell , chemistry , in vitro , biology , immunology , biochemistry , botany , germination
Targeted immunomodulation of dendritic cells (DCs) in vivo will enable manipulation of T-cell priming and amplification of anticancer immune responses, but a general strategy has been lacking. Here we show that DCs concentrated by a biomaterial can be metabolically labelled with azido groups in situ, which allows for their subsequent tracking and targeted modulation over time. Azido-labelled DCs were detected in lymph nodes for weeks, and could covalently capture dibenzocyclooctyne (DBCO)-bearing antigens and adjuvants via efficient Click chemistry for improved antigen-specific CD8 + T-cell responses and antitumour efficacy. We also show that azido labelling of DCs allowed for in vitro and in vivo conjugation of DBCO-modified cytokines, including DBCO-IL-15/IL-15Rα, to improve priming of antigen-specific CD8 + T cells. This DC labelling and targeted modulation technology provides an unprecedented strategy for manipulating DCs and regulating DC-T-cell interactions in vivo.