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Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients

BACKGROUND: Glioblastoma is the most common and malignant brain tumor in adults. Glioblastoma is usually fatal 12–15 months after diagnosis and the current possibilities in therapy are mostly only palliative. Therefore, new forms of diagnosis and therapy are urgently needed. Since tumor-associated m...

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Autores principales: Busch, Svenja, Talamini, Marina, Brenner, Steffen, Abdulazim, Amr, Hänggi, Daniel, Neumaier, Michael, Seiz-Rosenhagen, Marcel, Fuchs, Tina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545295/
https://www.ncbi.nlm.nih.gov/pubmed/31155685
http://dx.doi.org/10.1186/s40169-019-0235-8
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author Busch, Svenja
Talamini, Marina
Brenner, Steffen
Abdulazim, Amr
Hänggi, Daniel
Neumaier, Michael
Seiz-Rosenhagen, Marcel
Fuchs, Tina
author_facet Busch, Svenja
Talamini, Marina
Brenner, Steffen
Abdulazim, Amr
Hänggi, Daniel
Neumaier, Michael
Seiz-Rosenhagen, Marcel
Fuchs, Tina
author_sort Busch, Svenja
collection PubMed
description BACKGROUND: Glioblastoma is the most common and malignant brain tumor in adults. Glioblastoma is usually fatal 12–15 months after diagnosis and the current possibilities in therapy are mostly only palliative. Therefore, new forms of diagnosis and therapy are urgently needed. Since tumor-associated macrophages are key players in tumor progression and survival there is large potential in investigating their immunological characteristics in glioblastoma patients. Recent evidence shows the expression of variable immunoglobulins and TCRαβ in subpopulations of monocytes, in vitro polarized macrophages and macrophages in the tumor microenvironment. We set out to investigate the immunoglobulin sequences of circulating monocytes and tumor-associated macrophages from glioblastoma patients to evaluate their potential as novel diagnostic or therapeutic targets. RESULTS: We routinely find consistent expression of immunoglobulins in tumor-associated macrophages (TAM) and circulating monocytes from all glioblastoma patients analyzed in this study. However, the immunoglobulin repertoires of circulating monocytes and TAM are generally more restricted compared to B cells. Furthermore, the immunoglobulin expression in the macrophage populations negatively correlates with the tumor volume. Interestingly, the comparison of somatic mutations, V-chain usage, CDR3-length and the distribution of used heavy chain genes on the locus of chromosome 14 of the immunoglobulins from myeloid to B cells revealed virtually no differences. CONCLUSIONS: The investigation of the immunoglobulin repertoires from TAM and circulating monocytes in glioblastoma-patients revealed a negative correlation to the tumor volume, which could not be detected in the immunoglobulin repertoires of the patients’ B lymphocytes. Furthermore, the immunoglobulin repertoires of monocytes were more diverse than the repertoires of the macrophages in the tumor microenvironment from the same patients suggesting a tumor-specific immune response which could be advantageous for the use as diagnostic or therapeutic target. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40169-019-0235-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-65452952019-06-19 Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients Busch, Svenja Talamini, Marina Brenner, Steffen Abdulazim, Amr Hänggi, Daniel Neumaier, Michael Seiz-Rosenhagen, Marcel Fuchs, Tina Clin Transl Med Research BACKGROUND: Glioblastoma is the most common and malignant brain tumor in adults. Glioblastoma is usually fatal 12–15 months after diagnosis and the current possibilities in therapy are mostly only palliative. Therefore, new forms of diagnosis and therapy are urgently needed. Since tumor-associated macrophages are key players in tumor progression and survival there is large potential in investigating their immunological characteristics in glioblastoma patients. Recent evidence shows the expression of variable immunoglobulins and TCRαβ in subpopulations of monocytes, in vitro polarized macrophages and macrophages in the tumor microenvironment. We set out to investigate the immunoglobulin sequences of circulating monocytes and tumor-associated macrophages from glioblastoma patients to evaluate their potential as novel diagnostic or therapeutic targets. RESULTS: We routinely find consistent expression of immunoglobulins in tumor-associated macrophages (TAM) and circulating monocytes from all glioblastoma patients analyzed in this study. However, the immunoglobulin repertoires of circulating monocytes and TAM are generally more restricted compared to B cells. Furthermore, the immunoglobulin expression in the macrophage populations negatively correlates with the tumor volume. Interestingly, the comparison of somatic mutations, V-chain usage, CDR3-length and the distribution of used heavy chain genes on the locus of chromosome 14 of the immunoglobulins from myeloid to B cells revealed virtually no differences. CONCLUSIONS: The investigation of the immunoglobulin repertoires from TAM and circulating monocytes in glioblastoma-patients revealed a negative correlation to the tumor volume, which could not be detected in the immunoglobulin repertoires of the patients’ B lymphocytes. Furthermore, the immunoglobulin repertoires of monocytes were more diverse than the repertoires of the macrophages in the tumor microenvironment from the same patients suggesting a tumor-specific immune response which could be advantageous for the use as diagnostic or therapeutic target. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40169-019-0235-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2019-06-03 /pmc/articles/PMC6545295/ /pubmed/31155685 http://dx.doi.org/10.1186/s40169-019-0235-8 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research
Busch, Svenja
Talamini, Marina
Brenner, Steffen
Abdulazim, Amr
Hänggi, Daniel
Neumaier, Michael
Seiz-Rosenhagen, Marcel
Fuchs, Tina
Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
title Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
title_full Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
title_fullStr Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
title_full_unstemmed Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
title_short Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
title_sort circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545295/
https://www.ncbi.nlm.nih.gov/pubmed/31155685
http://dx.doi.org/10.1186/s40169-019-0235-8
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