www.oncotarget.com Oncotarget, 2021, Vol. 12, (No. 10), pp: 967-981 Research Paper Genome wide DNA methylation landscape reveals glioblastoma’s influence on epigenetic changes in tumor infiltrating CD4+ T cells Marpe Bam1,*, Sreenivasulu Chintala2,*, Kaleigh Fetcko2, Brooke Carmen Williamsen1, Seema Siraj1, Sheng Liu3, Jun Wan3, Xiaoling Xuei3, Yunlong Liu3, Adam T. Leibold2 and Mahua Dey1,2 1Department of Neurological Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA 2Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, IN, USA 3Department of Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA *These authors contributed equally to this work Correspondence to: Mahua Dey, email:
[email protected] Keywords: glioblastoma; malignant glioma; CD4+ T cell; DNA methylation; brain cancer Received: April 05, 2021 Accepted: April 19, 2021 Published: May 11, 2021 Copyright: © 2021 Bam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT CD4+ helper T (Th) cells play a critical role in shaping anti-tumor immunity by virtue of their ability to differentiate into multiple lineages in response to environmental cues. Various CD4+ lineages can orchestrate a broad range of effector activities during the initiation, expansion, and memory phase of endogenous anti-tumor immune response. In this clinical corelative study, we found that Glioblastoma (GBM) induces multi- and mixed-lineage immune response in the tumor microenvironment. Whole- genome bisulfite sequencing of tumor infiltrating and blood CD4+ T-cell from GBM patients showed 13571 differentially methylated regions and a distinct methylation pattern of methylation of tumor infiltrating CD4+ T-cells with significant inter- patient variability.