Specifically differentiated T cell subset promotes tumor immunity over fatal immunity

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

Research output: Contribution to journalArticle

22 Scopus citations

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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