PMID- 35740681 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 14 IP - 12 DP - 2022 Jun 19 TI - A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources. LID - 10.3390/cancers14123016 [doi] LID - 3016 AB - 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. FAU - Xiang, Haitao AU - Xiang H AUID- ORCID: 0000-0001-9971-1715 AD - College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. AD - BGI-Shenzhen, Shenzhen 518103, China. FAU - Zhang, Le AU - Zhang L AUID- ORCID: 0000-0002-2526-6484 AD - BGI-GenoImmune, BGI-Shenzhen, Shenzhen 518083, China. FAU - Bu, Fanyu AU - Bu F AUID- ORCID: 0000-0002-0875-7708 AD - BGI-Shenzhen, Shenzhen 518103, China. FAU - Guan, Xiangyu AU - Guan X AD - College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. AD - BGI-Shenzhen, Shenzhen 518103, China. FAU - Chen, Lei AU - Chen L AD - BGI-Shenzhen, Shenzhen 518103, China. FAU - Zhang, Haibo AU - Zhang H AD - BGI-Shenzhen, Shenzhen 518103, China. FAU - Zhao, Yuntong AU - Zhao Y AUID- ORCID: 0000-0002-5729-8747 AD - BGI-Shenzhen, Shenzhen 518103, China. FAU - Chen, Huanyi AU - Chen H AD - BGI-Shenzhen, Shenzhen 518103, China. FAU - Zhang, Weicong AU - Zhang W AD - College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. AD - BGI-Shenzhen, Shenzhen 518103, China. FAU - Li, Yijian AU - Li Y AD - College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. AD - BGI-Shenzhen, Shenzhen 518103, China. AD - Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, Shenzhen 518083, China. FAU - Lee, Leo Jingyu AU - Lee LJ AD - BGI-GenoImmune, BGI-Shenzhen, Shenzhen 518083, China. FAU - Mei, Zhanlong AU - Mei Z AD - BGI, Shenzhen 518083, China. FAU - Rao, Yuan AU - Rao Y AD - BGI, Shenzhen 518083, China. FAU - Gu, Ying AU - Gu Y AD - BGI-Shenzhen, Shenzhen 518103, China. AD - Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen 518120, China. FAU - Hou, Yong AU - Hou Y AD - BGI, Shenzhen 518083, China. FAU - Mu, Feng AU - Mu F AUID- ORCID: 0000-0002-0496-4996 AD - BGI, Shenzhen 518083, China. FAU - Dong, Xuan AU - Dong X AD - BGI-Shenzhen, Shenzhen 518103, China. AD - Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, Shenzhen 518083, China. LA - eng GR - JSGG20180508152912700/the Science, Technology and Innovation Commission of Shenzhen Municipality/ GR - 2020B1212070028/the Guangdong Enterprise Key Laboratory of Human Disease Genomics/ PT - Journal Article DEP - 20220619 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC9220843 OTO - NOTNLM OT - immunopeptidome OT - immunotherapy OT - mass spectrometry OT - neo-epitope COIS- The authors declare no conflict of interest. EDAT- 2022/06/25 06:00 MHDA- 2022/06/25 06:01 PMCR- 2022/06/19 CRDT- 2022/06/24 01:07 PHST- 2022/05/08 00:00 [received] PHST- 2022/06/09 00:00 [revised] PHST- 2022/06/13 00:00 [accepted] PHST- 2022/06/24 01:07 [entrez] PHST- 2022/06/25 06:00 [pubmed] PHST- 2022/06/25 06:01 [medline] PHST- 2022/06/19 00:00 [pmc-release] AID - cancers14123016 [pii] AID - cancers-14-03016 [pii] AID - 10.3390/cancers14123016 [doi] PST - epublish SO - Cancers (Basel). 2022 Jun 19;14(12):3016. doi: 10.3390/cancers14123016.