title: Optogenetic control of chemokine receptor signal and T-cell migration.
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.
authors.affiliation: Department of Microbiology and Immunology and David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642.
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Xu
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Hyun
authors.forename: Kihong
authors.initials: K
authors.lastname: Lim
authors.forename: Hyunwook
authors.initials: H
authors.lastname: Lee
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Cummings
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gerber
authors.forename: Seyeon
authors.initials: S
authors.lastname: Bae
authors.forename: Thomas Yoonsang
authors.initials: TY
authors.lastname: Cho
authors.forename: Edith M
authors.initials: EM
authors.lastname: Lord
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects; D016764:Cell Polarity / Q000276:immunology / Q000528:radiation effects; D007167:Immunotherapy; D008027:Light; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D062308:Optogenetics; D015202:Protein Engineering; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D019718:Receptors, CXCR4
keywords: CD8; chemotaxis; multiphoton microscopy; tumor immunology
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