Dataset Information

Reshaping of the MHC-I ligandome in response to reovirus-based cancer immunotherapy

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Patrick Murphy

LAB HEAD: Shashi Gujar

PROVIDER: PXD013066 | Pride | 2019-05-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	159302_z00720mouse_reomouse_reo.mzid.gz	Mzid
	159302_z00720mouse_reomouse_reo.pride.mztab.gz	Mztab
	159303_z00721mouse_reomouse_reo.mzid.gz	Mzid
	159303_z00721mouse_reomouse_reo.pride.mztab.gz	Mztab
	159304_z00722mouse_reomouse_reo.mzid.gz	Mzid

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Publications

Therapy-Induced MHC I Ligands Shape Neo-Antitumor CD8 T Cell Responses during Oncolytic Virus-Based Cancer Immunotherapy.

Murphy J Patrick JP Kim Youra Y Clements Derek R DR Konda Prathyusha P Schuster Heiko H Kowalewski Daniel J DJ Paulo Joao A JA Cohen Alejandro M AM Stevanovic Stefan S Gygi Steven P SP Gujar Shashi S

Journal of proteome research 20190529 6

Oncolytic viruses (OVs), known for their cancer-killing characteristics, also 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 determine ...[more]

PMID: 31095916

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