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

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...

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Published inCancers Vol. 14; no. 12; p. 3016
Main Authors Xiang, Haitao, Zhang, Le, Bu, Fanyu, Guan, Xiangyu, Chen, Lei, Zhang, Haibo, Zhao, Yuntong, Chen, Huanyi, Zhang, Weicong, Li, Yijian, Lee, Leo Jingyu, Mei, Zhanlong, Rao, Yuan, Gu, Ying, Hou, Yong, Mu, Feng, Dong, Xuan
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 19.06.2022
MDPI
Subjects
Antigen (tumor-associated)
Antigens
Antitumor activity
Cancer
Cancer immunotherapy
Colorectal cancer
Colorectal carcinoma
Epitopes
Genomes
Genomics
Histocompatibility antigen HLA
Immunotherapy
Integrated approach
Integration
Lymphocytes T
Mass spectrometry
Mass spectroscopy
Melanoma
Mutation
Neoantigens
Peptides
Scientific imaging
Tumor cells
United States > US
China
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Summary: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.
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These authors contributed equally to this work.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14123016