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Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia

Despite therapeutic advances, mortality of Acute Myeloid Leukemia (AML) is still high. Currently, the determination of prognosis which guides treatment decisions mainly relies on genetic markers. Besides molecular mechanisms, the ability of malignant cells to evade immune surveillance influences the...

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Autores principales: Marconato, Maddalena, Kauer, Joseph, Salih, Helmut R., Märklin, Melanie, Heitmann, Jonas S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508266/
https://www.ncbi.nlm.nih.gov/pubmed/36151238
http://dx.doi.org/10.1038/s41598-022-19972-1
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author Marconato, Maddalena
Kauer, Joseph
Salih, Helmut R.
Märklin, Melanie
Heitmann, Jonas S.
author_facet Marconato, Maddalena
Kauer, Joseph
Salih, Helmut R.
Märklin, Melanie
Heitmann, Jonas S.
author_sort Marconato, Maddalena
collection PubMed
description Despite therapeutic advances, mortality of Acute Myeloid Leukemia (AML) is still high. Currently, the determination of prognosis which guides treatment decisions mainly relies on genetic markers. Besides molecular mechanisms, the ability of malignant cells to evade immune surveillance influences the disease outcome and, among others, the expression of checkpoints modulators contributes to this. In AML, functional expression of the checkpoint molecule OX40 was reported, but the prognostic relevance of OX40 and its ligand OX40L axis has so far not been investigated. Here we described expression and prognostic relevance of the checkpoint modulators OX40 and OX40L, analyzed on primary AML cells obtained from 92 therapy naïve patients. Substantial expression of OX40 and OX40L on AML blasts was detected in 29% and 32% of the investigated subjects, respectively, without correlation between the expression of the receptor and its ligand. Whereas OX40L expression was not associated with different survival, patients with high expression levels of the receptor (OX40(high)) on AML blasts survived significantly shorter than OX40(low) patients (p = 0.009, HR 0.46, 95% CI 0.24–0.86), which identifies OX40 as novel prognostic marker and a potential therapeutic target in AML patients.
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spelling pubmed-95082662022-09-25 Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia Marconato, Maddalena Kauer, Joseph Salih, Helmut R. Märklin, Melanie Heitmann, Jonas S. Sci Rep Article Despite therapeutic advances, mortality of Acute Myeloid Leukemia (AML) is still high. Currently, the determination of prognosis which guides treatment decisions mainly relies on genetic markers. Besides molecular mechanisms, the ability of malignant cells to evade immune surveillance influences the disease outcome and, among others, the expression of checkpoints modulators contributes to this. In AML, functional expression of the checkpoint molecule OX40 was reported, but the prognostic relevance of OX40 and its ligand OX40L axis has so far not been investigated. Here we described expression and prognostic relevance of the checkpoint modulators OX40 and OX40L, analyzed on primary AML cells obtained from 92 therapy naïve patients. Substantial expression of OX40 and OX40L on AML blasts was detected in 29% and 32% of the investigated subjects, respectively, without correlation between the expression of the receptor and its ligand. Whereas OX40L expression was not associated with different survival, patients with high expression levels of the receptor (OX40(high)) on AML blasts survived significantly shorter than OX40(low) patients (p = 0.009, HR 0.46, 95% CI 0.24–0.86), which identifies OX40 as novel prognostic marker and a potential therapeutic target in AML patients. Nature Publishing Group UK 2022-09-23 /pmc/articles/PMC9508266/ /pubmed/36151238 http://dx.doi.org/10.1038/s41598-022-19972-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Marconato, Maddalena
Kauer, Joseph
Salih, Helmut R.
Märklin, Melanie
Heitmann, Jonas S.
Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia
title Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia
title_full Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia
title_fullStr Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia
title_full_unstemmed Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia
title_short Expression of the immune checkpoint modulator OX40 indicates poor survival in acute myeloid leukemia
title_sort expression of the immune checkpoint modulator ox40 indicates poor survival in acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508266/
https://www.ncbi.nlm.nih.gov/pubmed/36151238
http://dx.doi.org/10.1038/s41598-022-19972-1
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