Cai Yangyang, Li Donghao, Lv Dezhong, Yu Jiaxin, Ma Yingying, Jiang Tiantongfei, Ding Na, Liu Zhigang, Li Yongsheng, Xu Juan
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province, 150001, China.
Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Guangzhou, China.
Sci Data. 2024 Aug 1;11(1):831. doi: 10.1038/s41597-024-03660-y.
Identification of tumor neoantigens is indispensable for the development of cancer immunotherapies. However, we are still lacking knowledge about the potential neoantigens derived from sequences outside protein-coding regions. Here, we comprehensively characterized the immunopeptidome landscape by integrating multi-omics data in acute myeloid leukemia (AML). Both canonical and non-canonical MHC-associated peptides (MAPs) in AML were identified. We found that the quality and characteristics of ncMAPs are comparable or superior to cMAPs, suggesting ncMAPs are indispensable sources for tumor neoantigens. We further proposed a computational framework to prioritize the neoantigens by integrating additional transcriptome and immunopeptidome in normal tissues. Notably, 6 of prioritized 13 neoantigens were derived from ncMAPs. The expressions of corresponding source genes are highly related to infiltrations of immune cells. Finally, a risk model was developed, which exhibited good performance for clinical prognosis in AML. Our findings expand potential cancer immunotherapy targets and provide in-depth insights into AML treatment, laying a new foundation for precision therapies in AML.
肿瘤新抗原的鉴定对于癌症免疫疗法的发展至关重要。然而，我们仍然缺乏关于源自蛋白质编码区域之外序列的潜在新抗原的知识。在这里，我们通过整合急性髓系白血病（AML）中的多组学数据全面表征了免疫肽组图谱。鉴定出了AML中的经典和非经典MHC相关肽（MAP）。我们发现非经典MAP（ncMAP）的质量和特征与经典MAP（cMAP）相当或更优，表明ncMAP是肿瘤新抗原不可或缺的来源。我们进一步提出了一个计算框架，通过整合正常组织中的额外转录组和免疫肽组来对新抗原进行优先级排序。值得注意的是，在13个优先级新抗原中有6个源自ncMAP。相应源基因的表达与免疫细胞浸润高度相关。最后，开发了一个风险模型，该模型在AML临床预后方面表现良好。我们的发现扩展了潜在的癌症免疫治疗靶点，并为AML治疗提供了深入见解，为AML的精准治疗奠定了新基础。
