Specifically differentiated T cell subset promotes tumor immunity over fatal immunity

Abdulraouf Ramadan, Brad Griesenauer, Djamilatou Adom, Reuben Kapur, Helmut Hanenberg, Chen Liu, Mark Kaplan, Sophie Paczesny

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9IL-33 cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9IL-33 cells offers an attractive approach for separating GVL activity from GVHD.

Original languageEnglish (US)
Pages (from-to)3577-3596
Number of pages20
JournalJournal of Experimental Medicine
Volume214
Issue number12
DOIs
StatePublished - Dec 1 2017

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T-Lymphocyte Subsets
Immunity
Graft vs Host Disease
Transplants
Leukemia
Neoplasms
T-Lymphocytes
Interleukin-9
Adoptive Transfer
Hematologic Neoplasms
Acute Myeloid Leukemia
Population

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Specifically differentiated T cell subset promotes tumor immunity over fatal immunity. / Ramadan, Abdulraouf; Griesenauer, Brad; Adom, Djamilatou; Kapur, Reuben; Hanenberg, Helmut; Liu, Chen; Kaplan, Mark; Paczesny, Sophie.

In: Journal of Experimental Medicine, Vol. 214, No. 12, 01.12.2017, p. 3577-3596.

Research output: Contribution to journalArticle

Ramadan, Abdulraouf ; Griesenauer, Brad ; Adom, Djamilatou ; Kapur, Reuben ; Hanenberg, Helmut ; Liu, Chen ; Kaplan, Mark ; Paczesny, Sophie. / Specifically differentiated T cell subset promotes tumor immunity over fatal immunity. In: Journal of Experimental Medicine. 2017 ; Vol. 214, No. 12. pp. 3577-3596.
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