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.

转座因子 (TE) 中的隐蔽启动子可以在肿瘤中转录重新激活，以产生新的 TE 嵌合转录物，从而产生免疫原性抗原。我们对 33 种 TCGA 肿瘤类型、30 种 GTEx 成体组织和 675 种癌细胞系中的这些 TE 扩展事件进行了全面筛选，并确定了 1,068 种 TE 扩展候选物，这些候选物有可能产生共享的肿瘤特异性 TE 嵌合抗原（TS-TEA） ). 全裂解物和 HLA-pulldown 质谱数据证实 TS-TEA 存在于癌细胞表面。此外，我们重点介绍了从 TE 启动子转录的肿瘤特异性膜蛋白，这些启动子构成了癌细胞细胞外表面的异常表位。共，