PLZF confers effector functions to donor T cells that preserve graft-versus-tumor effects while attenuating GVHD Journal Article

Authors: Ghosh, A.; Holland, A. M.; Dogan, Y.; Yim, N. L.; Rao, U. K.; Young, L. F.; West, M. L.; Singer, N. V.; Lee, H.; Na, I. K.; Tsai, J. J.; Jenq, R. R.; Penack, O.; Hanash, A. M.; Lezcano, C.; Murphy, G. F.; Liu, C.; Sadelain, M.; Sauer, M. G.; Sant'angelo, D.; van den Brink, M. R. M.
Article 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. © 2013 American Association for Cancer Research.
Keywords: controlled study; protein expression; survival rate; transplantation, homologous; unclassified drug; nonhuman; flow cytometry; protein function; t lymphocyte; t-lymphocytes; protein analysis; animal cell; mouse; animals; mice; steady state; animal experiment; animal model; transcription factor; mice, inbred balb c; mice, inbred c57bl; th2 cell; lymphocyte activation; lymphocyte culture test, mixed; hematologic malignancy; cd4+ t lymphocyte; kruppel-like transcription factors; graft versus host reaction; neoplasms, experimental; adoptive transfer; cytokine production; th1 cell; cell stimulation; bone marrow transplantation; graft vs host disease; chemokine receptor ccr7; graft versus leukemia effect; graft vs tumor effect; cell expansion; graft recipient; mixed lymphocyte reaction; natural killer t cell; alloimmunity; promyelocytic leukemia zinc finger; lymphocyte function associated antigen 1; lymphocyte transfer; cytokine response
Journal Title: Cancer Research
Volume: 73
Issue: 15
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2013-08-01
Start Page: 4687
End Page: 4696
Language: English
DOI: 10.1158/0008-5472.can-12-4699
PROVIDER: scopus
PMCID: PMC3732814
PUBMED: 23733752
Notes: --- - "Export Date: 4 September 2013" - "CODEN: CNREA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Alan M Hanash
    81 Hanash
  2. Robert R Jenq
    102 Jenq
  3. Michel W J Sadelain
    452 Sadelain
  4. Yildirim Dogan
    13 Dogan
  5. Jennifer Tsai
    44 Tsai
  6. Arnab Ghosh
    39 Ghosh
  7. Uttam Keshav Rao
    28 Rao
  8. Nury Yim
    25 Yim
  9. Amanda M Holland
    52 Holland
  10. Lauren Young
    39 Young
  11. Natalie Singer
    24 Singer
  12. Mallory Lia West
    24 West
  13. Hae Lee
    1 Lee