한빛사논문
- 조회177
H. Josh Jang 1,2,3,8, Nakul M. Shah 1,2,8, Ju Heon Maeng 1,2,8, Yonghao Liang 1,2,8, Noah L. Basri 1,2, Jiaxin Ge 1,2, Xuan Qu 1,2, Tatenda Mahlokozera 4, Shin-Cheng Tzeng 5, Russell B. Williams 5, Michael J. Moore 1,2, Devi Annamalai 4, Justin Y. Chen 1,2, Hyung Joo Lee 1,2, Patrick A. DeSouza 4, Daofeng Li 1,2, Xiaoyun Xing 1,2, Albert H. Kim 4,6,* & Ting Wang 1,2,7,*
1Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
2The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
3Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
4Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO, USA.
5Donald Danforth Plant Science Center, St. Louis, MO, USA.
6The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
7McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
8These authors contributed equally: H. Josh Jang, Nakul M. Shah, Ju Heon Maeng, Yonghao Liang.
*Corresponding authors: correspondence to Albert H. Kim or Ting Wang
Abstract
Inhibiting epigenetic modulators can transcriptionally reactivate transposable elements (TEs). These TE transcripts often generate unique peptides that can serve as immunogenic antigens for immunotherapy. Here, we ask whether TEs activated by epigenetic therapy could appreciably increase the antigen repertoire in glioblastoma, an aggressive brain cancer with low mutation and neoantigen burden. We treated patient-derived primary glioblastoma stem cell lines, an astrocyte cell line and primary fibroblast cell lines with epigenetic drugs, and identified treatment-induced, TE-derived transcripts that are preferentially expressed in cancer cells. We verified that these transcripts could produce human leukocyte antigen class I-presented antigens using liquid chromatography with tandem mass spectrometry pulldown experiments. Importantly, many TEs were also transcribed, even in proliferating nontumor cell lines, after epigenetic therapy, which suggests that targeted strategies like CRISPR-mediated activation could minimize potential side effects of activating unwanted genomic regions. The results highlight both the need for caution and the promise of future translational efforts in harnessing treatment-induced TE-derived antigens for targeted immunotherapy.
논문정보
- Research article
- 2024년 09월 (BRIC 등록일 2024-09-04)
- 국외 연구진
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