美国圣路易斯华盛顿大学Ting Wang研究团队发现，泛癌分析确定源自可转座元件的肿瘤特异性抗原。该项研究成果发表在2023年3月27日在线发表在《自然—遗传学》杂志上。
研究人员在33个TCGA肿瘤类型、30个GTEx成人组织和675个癌症细胞系中对这些可转座元件（TE）外显事件进行了全面的筛选，并确定了1068个TE候选者，它们有可能产生共享的肿瘤特异性TE嵌合抗原（TS-TEA）。全细胞裂解物和HLA-pulldown质谱数据证实，TS-TEA呈现在癌细胞的表面。此外，研究人员强调了由TE启动子转录的肿瘤特异性膜蛋白，它们构成了癌细胞外表面的异常表位。总的来说，研究人员展示了TS-TEA和非典型膜蛋白在泛癌中的高流行率，这些膜蛋白有可能被治疗性地利用和靶向。
据介绍，TE内的隐蔽启动子在肿瘤中可被转录重新激活，产生新的TE-嵌合转录物，从而导致免疫原性抗原。
附：英文原文
Title: Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements
Author: Shah, Nakul M., Jang, H. Josh, Liang, Yonghao, Maeng, Ju Heon, Tzeng, Shin-Cheng, Wu, Angela, Basri, Noah L., Qu, Xuan, Fan, Changxu, Li, Amy, Katz, Benjamin, Li, Daofeng, Xing, Xiaoyun, Evans, Bradley S., Wang, Ting
Issue&Volume: 2023-03-27
Abstract: Cryptic promoters within transposable elements (TEs) can be transcriptionally reactivated in tumors to create new TE-chimeric transcripts, which can produce immunogenic antigens. We performed a comprehensive screen for these TE exaptation events in 33 TCGA tumor types, 30 GTEx adult tissues and 675 cancer cell lines, and identified 1,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Whole-lysate and HLA-pulldown mass spectrometry data confirmed that TS-TEAs are presented on the surface of cancer cells. In addition, we highlight tumor-specific membrane proteins transcribed from TE promoters that constitute aberrant epitopes on the extracellular surface of cancer cells. Altogether, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that could potentially be therapeutically exploited and targeted.
DOI: 10.1038/s41588-023-01349-3
Source: https://www.nature.com/articles/s41588-023-01349-3
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
