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Article

Epigenetic Suppression of the IL-7 Pathway in Progressive Glioblastoma

1
Szentagothai Research Center, University of Pecs, 7624 Pecs, Hungary
2
Department of Laboratory Medicine, University of Pecs, School of Medicine, Clinical Center, 7624 Pecs, Hungary
3
Department of Pathology, University of Pecs, School of Medicine, Clinical Center, 7624 Pecs, Hungary
4
Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Sonia Emanuele
Biomedicines 2022, 10(9), 2174; https://doi.org/10.3390/biomedicines10092174
Received: 13 August 2022 / Revised: 26 August 2022 / Accepted: 30 August 2022 / Published: 2 September 2022
Background: Immune evasion in glioblastoma (GBM) shields cancer cells from cytotoxic immune response. Methods: We investigated CpG methylation in promoters, genes, and pathways in 22 pairs of formalin-fixed paraffin-embedded sequential (FFPE) GBM using restricted resolution bisulfite sequencing (RRBS) and bioinformatic analyses. Results: Gene ontology revealed hypermethylation in elements of the innate and adaptive immune system when recurrent GBM samples (GBMrec) were compared to control (CG) and primary GBM samples (GBMprim). Higher methylation levels of the IL-7 signaling pathway and response to IL-7 were found in GBMrec suggesting a progressive blockade of the IL-7 driven T cell response in sequential GBM. Analyses of the Cancer Genome Atlas array-based data confirmed hypermethylation of the IL-7 pathway in recurrent compared with primary GBM. We also quantified DNA CpG methylation in promoter and gene regions of the IL-7 ligand and IL-7 α-receptor subunit in individual samples of a large RRBS-based sequential cohort of GBM in a Viennese database and found significantly higher methylation levels in the IL-7 receptor α-subunit in GBMrec compared with GBMprim. Conclusions: This study revealed the progressive suppression of the IL-7 receptor-mediated pathway as a means of immune evasion by GBM and thereby highlighted it as a new treatment target. View Full-Text
Keywords: glioblastoma; immune evasion; epigenomics; CpG methylation; interleukin 7 pathway glioblastoma; immune evasion; epigenomics; CpG methylation; interleukin 7 pathway
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MDPI and ACS Style

Tompa, M.; Kraboth, Z.; Galik, B.; Kajtar, B.; Gyenesei, A.; Kalman, B. Epigenetic Suppression of the IL-7 Pathway in Progressive Glioblastoma. Biomedicines 2022, 10, 2174. https://doi.org/10.3390/biomedicines10092174

AMA Style

Tompa M, Kraboth Z, Galik B, Kajtar B, Gyenesei A, Kalman B. Epigenetic Suppression of the IL-7 Pathway in Progressive Glioblastoma. Biomedicines. 2022; 10(9):2174. https://doi.org/10.3390/biomedicines10092174

Chicago/Turabian Style

Tompa, Marton, Zoltan Kraboth, Bence Galik, Bela Kajtar, Attila Gyenesei, and Bernadette Kalman. 2022. "Epigenetic Suppression of the IL-7 Pathway in Progressive Glioblastoma" Biomedicines 10, no. 9: 2174. https://doi.org/10.3390/biomedicines10092174

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