Genome-wide DNA methylation pattern uncovers glioblastoma's impact on cellular makeup
A recent study, published in the peer-reviewed open access biomedical journal Oncotarget, has shed light on the complex relationship between glioblastoma (GBM) and CD4+ T cells. The study, titled "Genome wide DNA methylation landscape reveals glioblastoma's influence on epigenetic changes in tumor infiltrating CD4+ T cells," was led by research teams at the University of Wisconsin-Madison and the Indiana University School of Medicine.
The findings suggest that GBM might be influencing the state of tumor infiltrating CD4+ T cells by epigenetic modification in the form of DNA methylation of key immune function regulating genes. This methylation, the study found, influences the fate of helper T cells in the GBM tumor microenvironment (TME).
The Dey Research Team, one of the key contributors to the study, concluded that differential DNA methylation patterns might influence gene expression in tumor infiltrating CD4+ T cells as compared to circulating blood CD4+ T cells in GBM patients. The study observed differential methylation of gene sets specific for CD4 T cells including Th1, Th2, Th17, and iTregs in GBM tumors, although with significant interpatient variability.
The study found differential methylation status of several genes involved in CD4 differentiation and function, including TBX21, GATA3, RORC, FOXP3, IL10, and IFNG in tumor CD4 T-cells. Whole-genome bisulfite sequencing was used to identify 13,571 differentially methylated regions in CD4 T-cells from GBM patients, with most of these regions concentrated around the transcription start site (TSS).
These methylation changes, the study found, resulted in transcriptomic changes with 341 differentially expressed genes in CD4 tumor infiltrating T-cells compared to blood. The study also observed dysregulation of several ligands of T cell function genes in GBM tissue corresponding to the T-cell receptors that were dysregulated in tumor infiltrating CD4 T-cells.
Correspondence for the article can be directed to Mahua Dey at [email protected]. Oncotarget, the journal that published the study, can be found at https://www.ImpactJournals.com or connected with at @ImpactJrnls. The article can be found at its full text at https://www.oncotarget.com/article/27955/text/ and more information about Oncotarget can be found at https://www.oncotarget.com.
The GBM tumor microenvironment is known to be extremely immunosuppressive, with properties including impaired cellular immunity, high levels of TGFβ, expression of several inhibitory ligands, immune checkpoints expression, and increased infiltration of immunosuppressive cells. The findings of this study provide valuable insights into the complex interactions between GBM and the immune system, which could lead to the development of new treatment strategies for this devastating brain cancer.
