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

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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., Holland, A.M., Dogan, Y., Yim, N., Rao, U.K., Young, L.F., West, M.L., Singer, N.V., Lee, H., Na, I.K., Tsai, J.J., Jenq, R., Penack, O., Hanash, A.M., Lezcano, C., Murphy, G.F., Liu, C., Sadelain, M., Sauer, M.G., 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
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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