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Specifically differentiated T cell subset promotes tumor immunity over fatal immunity

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 atta...

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Autores principales: Ramadan, Abdulraouf, Griesenauer, Brad, Adom, Djamilatou, Kapur, Reuben, Hanenberg, Helmut, Liu, Chen, Kaplan, Mark H., Paczesny, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716032/
https://www.ncbi.nlm.nih.gov/pubmed/29038366
http://dx.doi.org/10.1084/jem.20170041
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author Ramadan, Abdulraouf
Griesenauer, Brad
Adom, Djamilatou
Kapur, Reuben
Hanenberg, Helmut
Liu, Chen
Kaplan, Mark H.
Paczesny, Sophie
author_facet Ramadan, Abdulraouf
Griesenauer, Brad
Adom, Djamilatou
Kapur, Reuben
Hanenberg, Helmut
Liu, Chen
Kaplan, Mark H.
Paczesny, Sophie
author_sort Ramadan, Abdulraouf
collection PubMed
description 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 (T9(IL-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 T9(IL-33) cells offers an attractive approach for separating GVL activity from GVHD.
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spelling pubmed-57160322018-06-04 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 H. Paczesny, Sophie J Exp Med Research Articles 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 (T9(IL-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 T9(IL-33) cells offers an attractive approach for separating GVL activity from GVHD. The Rockefeller University Press 2017-12-04 /pmc/articles/PMC5716032/ /pubmed/29038366 http://dx.doi.org/10.1084/jem.20170041 Text en © 2017 Ramadan et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Ramadan, Abdulraouf
Griesenauer, Brad
Adom, Djamilatou
Kapur, Reuben
Hanenberg, Helmut
Liu, Chen
Kaplan, Mark H.
Paczesny, Sophie
Specifically differentiated T cell subset promotes tumor immunity over fatal immunity
title Specifically differentiated T cell subset promotes tumor immunity over fatal immunity
title_full Specifically differentiated T cell subset promotes tumor immunity over fatal immunity
title_fullStr Specifically differentiated T cell subset promotes tumor immunity over fatal immunity
title_full_unstemmed Specifically differentiated T cell subset promotes tumor immunity over fatal immunity
title_short Specifically differentiated T cell subset promotes tumor immunity over fatal immunity
title_sort specifically differentiated t cell subset promotes tumor immunity over fatal immunity
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716032/
https://www.ncbi.nlm.nih.gov/pubmed/29038366
http://dx.doi.org/10.1084/jem.20170041
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