PLZF confers effector functions to donor T cells that preserve graft-versus-tumor effects while attenuating GVHD.
| Autor: | Ghosh A; Departments of Immunology and Medicine, and Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ghosha1@mskcc.org, Holland AM, Dogan Y, Yim NL, Rao UK, Young LF, West ML, Singer NV, Lee H, Na IK, Tsai JJ, Jenq RR, Penack O, Hanash AM, Lezcano C, Murphy GF, Liu C, Sadelain M, Sauer MG, Sant'angelo D, van den Brink MR |
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| Jazyk: | angličtina |
| Zdroj: | Cancer research [Cancer Res] 2013 Aug 01; Vol. 73 (15), pp. 4687-96. Date of Electronic Publication: 2013 Jun 03. |
| DOI: | 10.1158/0008-5472.CAN-12-4699 |
| Abstrakt: | Efforts to limit GVHD mediated by alloreactive donor T cells after allogeneic bone marrow transplantation are limited by a concomitant decrease in graft-versus-tumor (GVT) activity and increased possibilities of tumor relapse. Using a novel approach, we adoptively transferred conventional T cells expressing the transcription factor promyelocytic leukemia zinc finger (PLZF), which confers effector properties resembling invariant natural killer T cells, such as copious production of cytokines under suboptimal stimulation. PLZF expression in T-cell allografts attenuates expansion of alloreactive T cells, leading to lower GVHD. Intact alloreactivity-driven antitumor cytokine responses result in preserved GVT effects, leading to improved survival. Our findings suggest that therapy with PLZF-overexpressing T cells would result in overall improved outcomes due to less GVHD and intact GVT effects. (©2013 AACR.) |
| Databáze: | MEDLINE |
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