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

Abstract 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-asso...

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Main Authors: Svenja Busch, Marina Talamini, Steffen Brenner, Amr Abdulazim, Daniel Hänggi, Michael Neumaier, Marcel Seiz-Rosenhagen, Tina Fuchs
Format: Article
Language:English
Published: Wiley 2019-06-01
Series:Clinical and Translational Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40169-019-0235-8
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author Svenja Busch
Marina Talamini
Steffen Brenner
Amr Abdulazim
Daniel Hänggi
Michael Neumaier
Marcel Seiz-Rosenhagen
Tina Fuchs
author_facet Svenja Busch
Marina Talamini
Steffen Brenner
Amr Abdulazim
Daniel Hänggi
Michael Neumaier
Marcel Seiz-Rosenhagen
Tina Fuchs
author_sort Svenja Busch
collection DOAJ
description Abstract 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.
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spelling doaj.art-c2e6b5bfd2854757b67f366a5d58b0b22022-12-21T23:39:04ZengWileyClinical and Translational Medicine2001-13262019-06-018111410.1186/s40169-019-0235-8Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patientsSvenja Busch0Marina Talamini1Steffen Brenner2Amr Abdulazim3Daniel Hänggi4Michael Neumaier5Marcel Seiz-Rosenhagen6Tina Fuchs7Institute for Clinical Chemistry, Medical Faculty Mannheim of Heidelberg UniversityInstitute for Clinical Chemistry, Medical Faculty Mannheim of Heidelberg UniversityDepartment of Neurosurgery, University Hospital Mannheim, Heidelberg UniversityDepartment of Neurosurgery, University Hospital Mannheim, Heidelberg UniversityDepartment of Neurosurgery, University Hospital Mannheim, Heidelberg UniversityInstitute for Clinical Chemistry, Medical Faculty Mannheim of Heidelberg UniversityDepartment of Neurosurgery, University Hospital Mannheim, Heidelberg UniversityInstitute for Clinical Chemistry, Medical Faculty Mannheim of Heidelberg UniversityAbstract 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.http://link.springer.com/article/10.1186/s40169-019-0235-8GlioblastomaImmunoglobulinsMonocytesTumor-associated macrophagesTumor volume
spellingShingle Svenja Busch
Marina Talamini
Steffen Brenner
Amr Abdulazim
Daniel Hänggi
Michael Neumaier
Marcel Seiz-Rosenhagen
Tina Fuchs
Circulating monocytes and tumor-associated macrophages express recombined immunoglobulins in glioblastoma patients
Clinical and Translational Medicine
Glioblastoma
Immunoglobulins
Monocytes
Tumor-associated macrophages
Tumor volume
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 Glioblastoma
Immunoglobulins
Monocytes
Tumor-associated macrophages
Tumor volume
url http://link.springer.com/article/10.1186/s40169-019-0235-8
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