A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources

Cancers

Feng Mu¹  Yuan Rao¹  Yong Hou¹  Zhanlong Mei¹  Le Zhang²  Leo Jingyu Lee²  Fanyu Bu³  Lei Chen³  Yuntong Zhao³  Ying Gu³  Haibo Zhang³  Huanyi Chen³  Xuan Dong³  Xiangyu Guan⁴  Weicong Zhang⁴  Yijian Li⁴  Haitao Xiang⁴ 

[1] BGI, Shenzhen 518083, China;BGI-GenoImmune, BGI-Shenzhen, Shenzhen 518083, China;BGI-Shenzhen, Shenzhen 518103, China;College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;

关键词: mass spectrometry;    immunopeptidome;    neo-epitope;    immunotherapy;   

DOI  :  10.3390/cancers14123016

来源: DOAJ

【 摘 要 】

Tumor-specific antigens can activate T cell-based antitumor immune responses and are ideal targets for cancer immunotherapy. However, their identification is still challenging. Although mass spectrometry can directly identify human leukocyte antigen (HLA) binding peptides in tumor cells, it focuses on tumor-specific antigens derived from annotated protein-coding regions constituting only 1.5% of the genome. We developed a novel proteogenomic integration strategy to expand the breadth of tumor-specific epitopes derived from all genomic regions. Using the colorectal cancer cell line HCT116 as a model, we accurately identified 10,737 HLA-presented peptides, 1293 of which were non-canonical peptides that traditional database searches could not identify. Moreover, we found eight tumor neo-epitopes derived from somatic mutations, four of which were not previously reported. Our findings suggest that this new proteogenomic approach holds great promise for increasing the number of tumor-specific antigen candidates, potentially enlarging the tumor target pool and improving cancer immunotherapy.

【 授权许可】

Unknown