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PLZF confers effector functions to donor T cells that preserve graft-versus-tumor effects while attenuating graft-versus-host-disease

Item Type:Article
Title:PLZF confers effector functions to donor T cells that preserve graft-versus-tumor effects while attenuating graft-versus-host-disease
Creators Name:Ghosh, A. and Holland, A.M. and Dogan, Y. and Yim, N. and Rao, U.K. and Young, L.F. and West, M.L. and Singer, N.V. and Lee, H. and Na, I.K. and Tsai, J.J. and Jenq, R. and Penack, O. and Hanash, A.M. and Lezcano, C. and Murphy, G.F. and Liu, C. and Sadelain, M. and Sauer, M.G. and Sant'Angelo, D. and van den Brink, M.R.M.
Abstract:Efforts to limit graft-versus-host disease (GVHD) mediated by alloreactive donor T cells after allogeneic bone marrow transplantation (allo-BMT) 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 (iNKT 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.
Keywords:Adoptive Transfer, Bone Marrow Transplantation, Experimental Neoplasms, Flow Cytometry, Graft vs Host Disease, Graft vs Tumor Effect, Homologous Transplantation, Kruppel-Like Transcription Factors, Lymphocyte Activation, Mixed Lymphocyte Culture Test, T-Lymphocytes, Animals, Mice
Source:Cancer Research
ISSN:0008-5472
Publisher:American Association for Cancer Research (U.S.A.)
Volume:73
Number:15
Page Range:4687-4696
Date:1 August 2013
Official Publication:https://doi.org/10.1158/0008-5472.CAN-12-4699
PubMed:View item in PubMed

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