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The effect of transforming growth factor-β2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma
Abstract
✓ This in vitro study was aimed at restitution of transforming growth factor (TGF)-β 2-mediated suppression of T-lymphocyte activation within malignant gliomas. In early-passage tumor cell cultures of two glioblastomas (HTZ-153 and HTZ-209) and one malignant astrocytoma classified as World Health Organization Grade III (HTZ-243), autologous peripheral blood mononuclear cells were activated by interleukin-lα and interleukin-2 in vitro (lymphokine-actived killer cells) and tested for cytotoxic and proliferative activity. In expression studies (Western blot and Northern hybridization) of all three tumors, TGF-β could be detected at the protein and messenger ribonucleic acid (mRNA) levels. A polyclonal anti-TGF-β neutralizing antibody did not enhance lymphocyte proliferation upon stimulation with tumor targets (3 H-thymidine incorporation) and slightly stimulated lymphocyte cytotoxicity against autologous target cells. Preincubation of target cells for 12 hours with TGF-β 2-specific phosphorothioate-anti-sense oligodeoxynucleotides (S-ODN's) did, however, enhance lymphocyte proliferation up to 2.5-fold and autologous tumor cytotoxicity up to 60%, compared to controls not treated with S-ODN's. Incubation of tumor cells with TGF-β 2-specific S-ODN's resulted in decreased TGF-β-specific immunoreactivity in cultured glioma cells, in reduced TGF-β 2 protein concentration (Western blot), and in a change in the expression pattern of TGF-β 2 mRNA's. These observations may have implications for in vivo and in vitro activation of a cellular immune response against autologous malignant glioma cells.
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“Additionally, they do not target TGF-β receptors specifically, since they equally effectively inhibit related type I receptors for several other TGF-β-related proteins, such as activin, nodal and myostatin293”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [293]
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Self-citation
Metadata
- Authors
- Jachimczak, P., Bogdahn, U., Schneider, J., Behl, C., Meixensberger, J., Apfel, R., Dörries, R., Schlingensiepen, K.-H., & Brysch, W.
- Affiliations
- University of Würzburg (DE)
- ORCID
- Behl, Christian
- Venue
- Journal of Neurosurgery
- Published
- 1993-06
- Volume
- 78
- Issue
- 6
- Pages
- 944-951
- ISSN
- 0022-3085 (ISSN-L)
- OpenAlex
- W2166484715
- Cited by
- 146
- References
- 48
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 4 · 2012: 6
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of neurosurgery (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- World Health Organization
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- transforming growth factor-beta2, high-grade glioma, glioblastoma, malignant astrocytoma, T cell activation, immunosuppression, lymphokine-activated killer cells, tumor cell killing, TGF-beta mRNA expression, autologous tumor cells, cell-mediated immunity
- MeSH terms
- Antigens, Neoplasm, Brain Neoplasms, Glioma, Humans, Immunity, Cellular, Leukocytes, Mononuclear, Phenotype, RNA, Neoplasm, T-Lymphocytes, Cytotoxic, Tumor Cells, Cultured, Blotting, Northern, Blotting, Western, Antigens, CD, Killer Cells, Lymphokine-Activated, Transforming Growth Factor beta, Oligonucleotides, Antisense, Immunocompromised Host
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