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Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects
CD137-targeting immune therapy, which activates anti-tumor T effector cell responses, seems to be an attractive concept in clinical oncology. Recent evidence has demonstrated that tumor cells besides T cells and antigen-presenting cells are able to express CD137 and CD137L. Here we aimed to identify...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844327/ https://www.ncbi.nlm.nih.gov/pubmed/31741755 http://dx.doi.org/10.1080/2162402X.2019.1651622 |
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author | Grimmig, Tanja Gasser, Martin Moench, Romana Zhu, Lang-Jing Nawalaniec, Karol Callies, Simone Wagner, Martin Polat, Buelent Mothi, Suraj Sarvode Luo, Yueming Ribas, Carmen M. Malafaia, Osvaldo Hsiao, Li-Li Waaga-Gasser, Ana Maria |
author_facet | Grimmig, Tanja Gasser, Martin Moench, Romana Zhu, Lang-Jing Nawalaniec, Karol Callies, Simone Wagner, Martin Polat, Buelent Mothi, Suraj Sarvode Luo, Yueming Ribas, Carmen M. Malafaia, Osvaldo Hsiao, Li-Li Waaga-Gasser, Ana Maria |
author_sort | Grimmig, Tanja |
collection | PubMed |
description | CD137-targeting immune therapy, which activates anti-tumor T effector cell responses, seems to be an attractive concept in clinical oncology. Recent evidence has demonstrated that tumor cells besides T cells and antigen-presenting cells are able to express CD137 and CD137L. Here we aimed to identify CD137/CD137L expression in established colon cancer cell lines and primary tumors (UICC stages I-IV) from patients with documented long-term follow-up. CD137/CD137L expression was highly upregulated in early to late-stage tumors while the inverse was observed in patient-derived peripheral blood mononuclear cells. High CD137L expression within primary tumors was mediated by tumor cells and significantly correlated with the occurrence of distant metastases and shortened survival in advanced stages of disease (UICC stage IV). Interestingly, induced tumor cell signaling via CD137L on its surface in vitro resulted in dual effects: (i) reduced tumor cell proliferation suggesting inhibitory signaling in all investigated cancers and (ii) increased epithelial-to-mesenchymal transition signaling events. Taken together CD137/CD137L expression was stage-dependently upregulated with shortened survival in patients with highly CD137L-expressing tumors. Our clinical and experimental data suggest that colon cancer cells predominantly express CD137L and thereby have negative impact on overall survival through a process of reverse signaling. Beside agonistic CD137 antibody therapy to foster T effector cell responses, CD137L-mediated intervention strategies may become instrumental to circumvent relapsed tumor growth through induced epithelial-to-mesenchymal transition and consecutive metastases formation. |
format | Online Article Text |
id | pubmed-6844327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-68443272019-11-18 Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects Grimmig, Tanja Gasser, Martin Moench, Romana Zhu, Lang-Jing Nawalaniec, Karol Callies, Simone Wagner, Martin Polat, Buelent Mothi, Suraj Sarvode Luo, Yueming Ribas, Carmen M. Malafaia, Osvaldo Hsiao, Li-Li Waaga-Gasser, Ana Maria Oncoimmunology Original Research CD137-targeting immune therapy, which activates anti-tumor T effector cell responses, seems to be an attractive concept in clinical oncology. Recent evidence has demonstrated that tumor cells besides T cells and antigen-presenting cells are able to express CD137 and CD137L. Here we aimed to identify CD137/CD137L expression in established colon cancer cell lines and primary tumors (UICC stages I-IV) from patients with documented long-term follow-up. CD137/CD137L expression was highly upregulated in early to late-stage tumors while the inverse was observed in patient-derived peripheral blood mononuclear cells. High CD137L expression within primary tumors was mediated by tumor cells and significantly correlated with the occurrence of distant metastases and shortened survival in advanced stages of disease (UICC stage IV). Interestingly, induced tumor cell signaling via CD137L on its surface in vitro resulted in dual effects: (i) reduced tumor cell proliferation suggesting inhibitory signaling in all investigated cancers and (ii) increased epithelial-to-mesenchymal transition signaling events. Taken together CD137/CD137L expression was stage-dependently upregulated with shortened survival in patients with highly CD137L-expressing tumors. Our clinical and experimental data suggest that colon cancer cells predominantly express CD137L and thereby have negative impact on overall survival through a process of reverse signaling. Beside agonistic CD137 antibody therapy to foster T effector cell responses, CD137L-mediated intervention strategies may become instrumental to circumvent relapsed tumor growth through induced epithelial-to-mesenchymal transition and consecutive metastases formation. Taylor & Francis 2019-09-06 /pmc/articles/PMC6844327/ /pubmed/31741755 http://dx.doi.org/10.1080/2162402X.2019.1651622 Text en © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Original Research Grimmig, Tanja Gasser, Martin Moench, Romana Zhu, Lang-Jing Nawalaniec, Karol Callies, Simone Wagner, Martin Polat, Buelent Mothi, Suraj Sarvode Luo, Yueming Ribas, Carmen M. Malafaia, Osvaldo Hsiao, Li-Li Waaga-Gasser, Ana Maria Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects |
title | Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects |
title_full | Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects |
title_fullStr | Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects |
title_full_unstemmed | Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects |
title_short | Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects |
title_sort | expression of tumor-mediated cd137 ligand in human colon cancer indicates dual signaling effects |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844327/ https://www.ncbi.nlm.nih.gov/pubmed/31741755 http://dx.doi.org/10.1080/2162402X.2019.1651622 |
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