PXD013066

PXD013066 is an original dataset announced via ProteomeXchange.

Title	Reshaping of the MHC-I ligandome in response to reovirus-based cancer immunotherapy
Description	Oncolytic viruses (OVs), known for their cancer-killing characteristics, overturn tumor-associated defects in antigen presentation through the MHC class I pathway and induce protective neo antitumor CD8 T cell responses. Nonetheless, whether OVs shape the tumor MHC-I ligandome remains unknown. Here, we investigated if an OV induces the presentation of novel MHC I-bound tumor antigens (termed tumor MHC-I ligands). Using comparative mass spectrometry (MS)-based MHC-I ligandomics, we determined differential tumor MHC-I ligand expression following treatment with oncolytic reovirus in a murine ovarian cancer model. In vitro we found that reovirus induces the presentation of tumor MHC-I ligands in cancer cells. Concurrent multiplexed quantitative proteomics revealed that the changes in tumor MHC-I ligand presentation were mostly independent of reovirus-induced alterations of their source proteins. In an in vivo model, tumor MHC-I ligands were induced by reovirus in tumors but also, more importantly, analysis of spleens (a source of antigen-presenting cells) showed exclusive induction of most MHC-I ligands occurred in tumor-bearing mice. Finally, IFNγ assays demonstrated immunogenicity of the reovirus-induced MHC-I ligands. OV-induced MHC-I responses may be exploited in combinatorial approaches to promote the efficacy of cancer immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2019-05-20
AnnouncementXML	Submission_2019-05-20_00:55:07.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD013066
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Patrick Murphy
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Oxidation; Carbamidomethyl; TMT
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-12 08:59:10	ID requested
⏵ 1	2019-05-20 00:55:08	announced

Murphy JP, Kim Y, Clements DR, Konda P, Schuster H, Kowalewski DJ, Paulo JA, Cohen AM, Stevanovic S, Gygi SP, Gujar S, Therapy-Induced MHC I Ligands Shape Neo-Antitumor CD8 T Cell Responses during Oncolytic Virus-Based Cancer Immunotherapy. J Proteome Res, 18(6):2666-2675(2019) [pubmed]

submitter keyword: Oncolytic virus, reovirus, cancer immunotherapy, mass spectrometry, MHC ligandome, CD8 T cell epitopes, antitumor immunity

Shashi Gujar
contact affiliation	Department of Pathology, Dalhousie University
contact email	shashi.gujar@dal.ca
lab head
Patrick Murphy
contact affiliation	Mass Spectrometry
contact email	patrick.murphy@dal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013066
     1. Label: PRIDE project
     2. Name: Reshaping of the MHC-I ligandome in response to reovirus-based cancer immunotherapy