한빛사 논문
Abstract
Yuexin Xua,b,1, Young-Min Hyuna,b,1, Kihong Limb, Hyunwook Leeb, Ryan J. Cummingsa, Scott A. Gerbera, Seyeon Baeb, Thomas Yoonsang Choc, Edith M. Lorda, and Minsoo Kima,b,2
aDepartment of Microbiology and Immunology and
bDavid H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642; and
cEdward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO 63104
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.
CD8, tumor immunology, chemotaxis, multiphoton microscopy
1Y.X. and Y.-M.H. contributed equally to this work.
2To whom correspondence should be addressed
Author contributions: Y.X., Y.-M.H., S.A.G., E.M.L., and M.K. designed research; Y.X., Y.-M.H., K.L., H.L., R.J.C., S.A.G., and S.B. performed research; T.Y.C. and E.M.L. contributed new reagents/analytic tools; Y.X., Y.-M.H., K.L., T.Y.C., and M.K. analyzed data; and Y.X., Y.-M.H., and M.K. wrote the paper.
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