PXD022949

PXD022949 is an original dataset announced via ProteomeXchange.

Title	Proteogenomic analysis unveils the HLA Class I presented immunopeptidome in melanoma and EGFR mutant lung adenocarcinoma
Description	Immune checkpoint inhibitor and adoptive lymphocyte transfer-based therapies have shown great therapeutic potential for cancers with high tumor mutation burden (TMB). Here, we employed mass spectrometry (MS)-based proteogenomic large-scale profiling to identify potential immunogenic human leukocyte antigen (HLA) Class ǀ-presented peptides in both melanoma, a “hot tumor” with high TMB, and EGFR mutant lung adenocarcinoma, a “cold tumor” with low TMB. We used cell line and patient-specific databases constructed using variants identified from whole-exome sequencing, as well as a de novo search algorithm from the PEAKS search algorithm to interrogate the mass spectrometry data of the Class I immunopeptidome. We identified 12 mutant neoantigens. Several classes of tumor-associated antigen-derived peptides were also identified. We constructed a cancer germline (CG) antigen database with 285 antigens and identified 42 Class I-presented CG antigens. We identified more than 1000 post-translationally modified (PTM) peptides representing 58 different PTMs. Our results suggest that PTMs play a critical role impacting HLA-binding affinity dramatically. Finally, leveraging de novo search and an annotated lncRNA database, we developed a novel non-canonical peptide discovery pipeline to identify 44 lncRNA-derived peptides that are presented by Class I. We validated MS/MS spectra of select peptides using synthetic peptides and performed HLA Class I binding assays to demonstrate binding of select neo-peptides and lncRNA-derived peptides to Class I proteins. In summary, we provide direct evidence of HLA Class I presentation of a large number of mutant and tumor-associated peptides for potential use as vaccine or adoptive cell therapy in melanoma and EGFR mutant lung cancer.
HostingRepository	PRIDE
AnnounceDate	2021-08-23
AnnouncementXML	Submission_2021-08-23_00:09:19.447.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022949
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Yue Qi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; amidated residue; phosphorylated residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-07 00:42:46	ID requested
⏵ 1	2021-08-23 00:09:20	announced

Qi YA, Maity TK, Cultraro CM, Misra V, Zhang X, Ade C, Gao S, Milewski D, Nguyen KD, Ebrahimabadi MH, Hanada KI, Khan J, Sahinalp C, Yang JC, Guha U, Proteogenomic Analysis Unveils the HLA Class I-Presented Immunopeptidome in Melanoma and EGFR-Mutant Lung Adenocarcinoma. Mol Cell Proteomics, 20():100136(2021) [pubmed]

submitter keyword: immunotherapy, HLA immunopeptidome, neoantigen, lung cancer, melanoma

Udayan Guha
contact affiliation	Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA 7Present address: Bristol Myers Squibb, Lawrenceville, NJ 08901, USA and Thoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
contact email	udayan.guha@nih.gov
lab head
Yue Qi
contact affiliation	National Cancer Institute/NIH
contact email	andy.qi@nih.gov
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022949
     1. Label: PRIDE project
     2. Name: Proteogenomic analysis unveils the HLA Class I presented immunopeptidome in melanoma and EGFR mutant lung adenocarcinoma