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 language | English (US) |
|---|---|
| Pages (from-to) | 3577-3596 |
| Number of pages | 20 |
| Journal | Journal of Experimental Medicine |
| Volume | 214 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Specifically differentiated T cell subset promotes tumor immunity over fatal immunity
AU - Ramadan, Abdulraouf
AU - Griesenauer, Brad
AU - Adom, Djamilatou
AU - Kapur, Reuben
AU - Hanenberg, Helmut
AU - Liu, Chen
AU - Kaplan, Mark
AU - Paczesny, Sophie
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85036501806&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85036501806&partnerID=8YFLogxK
U2 - 10.1084/jem.20170041
DO - 10.1084/jem.20170041
M3 - Article
C2 - 29038366
AN - SCOPUS:85036501806
VL - 214
SP - 3577
EP - 3596
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 12
ER -