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Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity()
OX40 and its ligand are members of the TNF/TNF receptor superfamily, which includes various molecules influencing cellular signaling and function of both tumor and immune cells. The ability of OX40 to promote proliferation and differentiation of activated T cells fueled present attempts to modulate...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175778/ https://www.ncbi.nlm.nih.gov/pubmed/30300827 http://dx.doi.org/10.1016/j.neo.2018.09.005 |
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author | Rothfelder, Kathrin Hagelstein, Ilona Roerden, Malte Blumenstock, Gunnar Hofmann, Martin Nuebling, Tina Jung, Gundram Salih, Helmut Rainer Dörfel, Daniela |
author_facet | Rothfelder, Kathrin Hagelstein, Ilona Roerden, Malte Blumenstock, Gunnar Hofmann, Martin Nuebling, Tina Jung, Gundram Salih, Helmut Rainer Dörfel, Daniela |
author_sort | Rothfelder, Kathrin |
collection | PubMed |
description | OX40 and its ligand are members of the TNF/TNF receptor superfamily, which includes various molecules influencing cellular signaling and function of both tumor and immune cells. The ability of OX40 to promote proliferation and differentiation of activated T cells fueled present attempts to modulate this immune checkpoint to reinforce antitumor immunity. While we recently found evidence for the involvement of OX40 in pathophysiology of acute myeloid leukemia including natural killer (NK) cell immunosurveillance, less is known on its role in acute lymphoblastic leukemia (ALL). In the present study, OX40 expression on ALL cells was significantly associated with positivity for the adverse risk factor BCR-ABL. In line, signaling via OX40 increased metabolic activity of primary ALL cells and resulted in release of cytokines involved in disease pathophysiology. Furthermore, interaction of ALL-expressed OX40 with its cognate ligand on NK cells stimulated ALL cell lysis. The data presented thus not only identify the yet unknown involvement of OX40/OX40L in ALL pathophysiology and NK cell immunosurveillance but also point to the necessity to thoroughly consider the consequences of modulating the OX40/OX40L molecule system beyond its effects on T cells when developing OX40-targeting approaches for cancer immunotherapy. |
format | Online Article Text |
id | pubmed-6175778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61757782018-10-10 Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity() Rothfelder, Kathrin Hagelstein, Ilona Roerden, Malte Blumenstock, Gunnar Hofmann, Martin Nuebling, Tina Jung, Gundram Salih, Helmut Rainer Dörfel, Daniela Neoplasia Original article OX40 and its ligand are members of the TNF/TNF receptor superfamily, which includes various molecules influencing cellular signaling and function of both tumor and immune cells. The ability of OX40 to promote proliferation and differentiation of activated T cells fueled present attempts to modulate this immune checkpoint to reinforce antitumor immunity. While we recently found evidence for the involvement of OX40 in pathophysiology of acute myeloid leukemia including natural killer (NK) cell immunosurveillance, less is known on its role in acute lymphoblastic leukemia (ALL). In the present study, OX40 expression on ALL cells was significantly associated with positivity for the adverse risk factor BCR-ABL. In line, signaling via OX40 increased metabolic activity of primary ALL cells and resulted in release of cytokines involved in disease pathophysiology. Furthermore, interaction of ALL-expressed OX40 with its cognate ligand on NK cells stimulated ALL cell lysis. The data presented thus not only identify the yet unknown involvement of OX40/OX40L in ALL pathophysiology and NK cell immunosurveillance but also point to the necessity to thoroughly consider the consequences of modulating the OX40/OX40L molecule system beyond its effects on T cells when developing OX40-targeting approaches for cancer immunotherapy. Neoplasia Press 2018-10-06 /pmc/articles/PMC6175778/ /pubmed/30300827 http://dx.doi.org/10.1016/j.neo.2018.09.005 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Rothfelder, Kathrin Hagelstein, Ilona Roerden, Malte Blumenstock, Gunnar Hofmann, Martin Nuebling, Tina Jung, Gundram Salih, Helmut Rainer Dörfel, Daniela Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity() |
title | Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity() |
title_full | Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity() |
title_fullStr | Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity() |
title_full_unstemmed | Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity() |
title_short | Expression of the Immune Checkpoint Modulator OX40 in Acute Lymphoblastic Leukemia Is Associated with BCR-ABL Positivity() |
title_sort | expression of the immune checkpoint modulator ox40 in acute lymphoblastic leukemia is associated with bcr-abl positivity() |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175778/ https://www.ncbi.nlm.nih.gov/pubmed/30300827 http://dx.doi.org/10.1016/j.neo.2018.09.005 |
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