PXD020224

PXD020224 is an original dataset announced via ProteomeXchange.

Title	Anti-tumor immunity induces the presentation of aberrant peptides in melanoma
Description	Many tumors escape by activating multiple cellular pathways that induce immunosuppression. One pivotal immune-suppressive mechanism is the production of tryptophan metabolites along the kynurenine pathway by IFNγ-induced IDO1 enzyme production 4-8. Phase III clinical trials using chemical inhibition of IDO1 in combination with PD1 pathway blockade, however, failed to improve melanoma treatment 9-12. This points at an incomplete understanding of the role of IDO1 and the consequent tryptophan degradation on mRNA translation and cancer progression. Here, we investigated the effects of prolonged IFNγ treatment on mRNA translation in melanoma cells by ribosome profiling. Surprisingly, we observed a massive accumulation of ribosomes ~20 amino acids downstream of tryptophan codons (termed here as W-Bumps) along with their expected stalling at the tryptophan codon itself. This indicated ribosomal bypass of the tryptophan codons in the absence of tryptophan. Detailed examination of W-Bumps position and its corresponding peptide sequences pinpointed towards ribosomal frameshifting events and their effects in the ribosome exit tunnel. In particular, W-Bumps strength was associated with the disorderedness level of potential out-of-frame peptides predicted downstream of tryptophan codons. Indeed, reporter assays demonstrated the induction of ribosomal frameshifting, and the generation of trans-frame proteins and their presentation at the cell surface after IFNγ treatment. Proteomics and immunopeptidomics analyses verified the production of IFNγ-induced trans-frame and out-of-frame aberrant peptides and their presentation on HLA class I molecules. Priming of naïve T cells from healthy donors with aberrant peptides resulted in identification of reactive, peptide-specific T cells. Altogether, our results suggest that IFNγ-induced IDO1-mediated tryptophan depletion plays a role in the immune recognition of melanoma cells by contributing to the diversity of the peptidome landscape, and by inducing the presentation of aberrant peptides.
HostingRepository	PRIDE
AnnounceDate	2020-12-04
AnnouncementXML	Submission_2021-02-16_22:41:09.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Onno Bleijerveld
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X; Orbitrap Fusion; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-06 15:07:49	ID requested
1	2020-12-04 06:02:21	announced
⏵ 2	2021-02-16 22:41:11	announced	2021-02-17: Updated publication reference for PubMed record(s): 33328638.

Bartok O, Pataskar A, Nagel R, Laos M, Goldfarb E, Hayoun D, Levy R, K, ö, rner PR, Kreuger IZM, Champagne J, Zaal EA, Bleijerveld OB, Huang X, Kenski J, Wargo J, Brandis A, Levin Y, Mizrahi O, Alon M, Lebon S, Yang W, Nielsen MM, Stern-Ginossar N, Altelaar M, Berkers CR, Geiger T, Peeper DS, Olweus J, Samuels Y, Agami R, Anti-tumour immunity induces aberrant peptide presentation in melanoma. Nature, 590(7845):332-337(2021) [pubmed]

submitter keyword: Melanoma, proteomics, immunopeptidomics, LC-MS/MS, aberrant peptides, tryptophan depletion, immune recognition

Reuven Agami
contact affiliation	Division of Oncogenomics, Oncode institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands;
contact email	r.agami@nki.nl
lab head
Onno Bleijerveld
contact affiliation	The Netherlands Cancer Institute
contact email	o.bleijerveld@nki.nl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/12/PXD020224

PRIDE project URI

• PRIDE
  1. PXD020224
     1. Label: PRIDE project
     2. Name: Anti-tumor immunity induces the presentation of aberrant peptides in melanoma