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Optogenetic control of chemokine receptor signal and T-cell migration

Authors
 Yuexin Xu  ;  Young-Min Hyun  ;  Kihong Lim  ;  Hyunwook Lee  ;  Ryan J. Cummings  ;  Scott A. Gerber  ;  Seyeon Bae  ;  Thomas Yoonsang Cho  ;  Edith M. Lord  ;  Minsoo Kim 
Citation
 Proceedings of the National Academy of Sciences of the United States of America, Vol.111(17) : 6371-6376, 2014 
Journal Title
 Proceedings of the National Academy of Sciences of the United States of America 
ISSN
 0027-8424 
Issue Date
2014
MeSH
Amino Acid Sequence ; Animals ; Cell Adhesion/radiation effects ; Cell Movement*/radiation effects ; Cell Polarity/immunology ; Cell Polarity/radiation effects ; Immunotherapy ; Light ; Mice ; Molecular Sequence Data ; Neoplasms/immunology ; Neoplasms/therapy ; Optogenetics* ; Protein Engineering ; Receptors, CXCR4/chemistry ; Receptors, CXCR4/metabolism* ; Signal Transduction/radiation effects ; T-Lymphocytes/cytology* ; T-Lymphocytes/immunology
Keywords
CD8 ; chemotaxis ; multiphoton microscopy ; tumor immunology
Abstract
Adoptive cell transfer of ex vivo-generated immune-promoting or tolerogenic T cells to either enhance immunity or promote tolerance in patients has been used with some success. However, effective trafficking of the transferred cells to the target tissue sites is the main barrier to achieving successful clinical outcomes. Here we developed a strategy for optically controlling T-cell trafficking using a photoactivatable (PA) chemokine receptor. Photoactivatable-chemokine C-X-C motif receptor 4 (PA-CXCR4) transmitted intracellular CXCR4 signals in response to 505-nm light. Localized activation of PA-CXCR4 induced T-cell polarization and directional migration (phototaxis) both in vitro and in vivo. Directing light onto the melanoma was sufficient to recruit PA-CXCR4-expressing tumor-targeting cytotoxic T cells and improved the efficacy of adoptive T-cell transfer immunotherapy, with a significant reduction in tumor growth in mice. These findings suggest that the use of photoactivatable chemokine receptors allows remotely controlled leukocyte trafficking with outstanding spatial resolution in tissues and may be feasible in other cell transfer therapies.
Files in This Item:
T201406301.pdf Download
DOI
10.1073/pnas.1319296111
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
현영민(Hyun, Young-Min) ORCID logo https://orcid.org/0000-0002-0567-2039
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/158594
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