Dataset Information

Proteogenomic analysis unveils the HLA Class I presented immunopeptidome in melanoma and EGFR mutant lung adenocarcinoma

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell Of Skin Gland, Lung, Epithelial Cell Of Lung

DISEASE(S): Lung Adenocarcinoma,Melanomatosis

SUBMITTER: Yue Andy Qi

LAB HEAD: Udayan Guha

PROVIDER: PXD022949 | Pride | 2021-08-23

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20180522_H1975_DMSO_Total_BioRep1_F1.index	Other
	20180522_H1975_DMSO_Total_BioRep1_F1.raw	Raw
	20180522_H1975_DMSO_Total_BioRep1_F10.index	Other
	20180522_H1975_DMSO_Total_BioRep1_F10.raw	Raw
	20180522_H1975_DMSO_Total_BioRep1_F11.index	Other

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Publications

Proteogenomic Analysis Unveils the HLA Class I-Presented Immunopeptidome in Melanoma and EGFR-Mutant Lung Adenocarcinoma.

Qi Yue A YA Maity Tapan K TK Cultraro Constance M CM Misra Vikram V Zhang Xu X Ade Catherine C Gao Shaojian S Milewski David D Nguyen Khoa D KD Ebrahimabadi Mohammad H MH Hanada Ken-Ichi KI Khan Javed J Sahinalp Cenk C Yang James C JC Guha Udayan U

Molecular & cellular proteomics : MCP 20210813

Immune checkpoint inhibitors and adoptive lymphocyte transfer-based therapies have shown great therapeutic potential in cancers with high tumor mutational burden (TMB), such as melanoma, but not in cancers with low TMB, such as mutant epidermal growth factor receptor (EGFR)-driven lung adenocarcinoma. Precision immunotherapy is an unmet need for most cancers, particularly for cancers that respond inadequately to immune checkpoint inhibitors. Here, we employed large-scale MS-based proteogenomic p ...[more]

PMID: 34391887

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