title: PLZF confers effector functions to donor T cells that preserve graft-versus-tumor effects while attenuating GVHD.
abstract: 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.
authors.affiliation: Departments of Immunology and Medicine, and Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ghosha1@mskcc.org
authors.forename: Arnab
authors.initials: A
authors.lastname: Ghosh
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Holland
authors.forename: Yildirim
authors.initials: Y
authors.lastname: Dogan
authors.forename: Nury L
authors.initials: NL
authors.lastname: Yim
authors.forename: Uttam K
authors.initials: UK
authors.lastname: Rao
authors.forename: Lauren F
authors.initials: LF
authors.lastname: Young
authors.forename: Mallory L
authors.initials: ML
authors.lastname: West
authors.forename: Natalie V
authors.initials: NV
authors.lastname: Singer
authors.forename: Hae
authors.initials: H
authors.lastname: Lee
authors.forename: Il-Kang
authors.initials: IK
authors.lastname: Na
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Tsai
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jenq
authors.forename: Olaf
authors.initials: O
authors.lastname: Penack
authors.forename: Alan M
authors.initials: AM
authors.lastname: Hanash
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lezcano
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Michel
authors.initials: M
authors.lastname: Sadelain
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sauer
authors.forename: Derek
authors.initials: D
authors.lastname: Sant'angelo
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D020350:Graft vs Tumor Effect / Q000276:immunology*; D051741:Kruppel-Like Transcription Factors / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014184:Transplantation, Homologous
chemical_list: D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse