Dataset Information

Neuroblastoma HLA class I Immunopeptidomics

ABSTRACT: We surveyed the immunopeptidome of neuroblastoma tumors to identify tumor-specific targets derived from non-mutated self proteins originating from core-regulatory circuit proteins.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell, Early Embryonic Cell, Kidney

DISEASE(S): Neuroblastoma

SUBMITTER: Mark Yarmarkovich

LAB HEAD: John M. Maris

PROVIDER: PXD027182 | Pride | 2021-08-11

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Mark_5ppm_0.02_1FDR_Area_NoMatching_PDX.mzML	Mzml
	Mark_5ppm_0.02_1FDR_Area_NoMatching_PDX.mzid.gz	Mzid
	Mark_5ppm_0.02_1FDR_Area_NoMatching_PDX_PSM.mzML	Mzml
	Mark_5ppm_0.02_1FDR_Area_NoMatching_PDX_PeptideSpectra.mzML	Mzml
	Mark_5ppm_0.02_1FDR_Area_NoMatching_Patient.mzML	Mzml

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Publications

Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs.

Yarmarkovich Mark M Marshall Quinlen F QF Warrington John M JM Premaratne Rasika R Farrel Alvin A Groff David D Li Wei W di Marco Moreno M Runbeck Erin E Truong Hau H Toor Jugmohit S JS Tripathi Sarvind S Nguyen Son S Shen Helena H Noel Tiffany T Church Nicole L NL Weiner Amber A Kendsersky Nathan N Martinez Dan D Weisberg Rebecca R Christie Molly M Eisenlohr Laurence L Bosse Kristopher R KR Dimitrov Dimiter S DS Stevanovic Stefan S Sgourakis Nikolaos G NG Kiefel Ben R BR Maris John M JM

Nature 20211103 7885

The majority of oncogenic drivers are intracellular proteins, thus constraining their immunotherapeutic targeting to mutated peptides (neoantigens) presented by individual human leukocyte antigen (HLA) allotypes<sup>1</sup>. However, most cancers have a modest mutational burden that is insufficient to generate responses using neoantigen-based therapies<sup>2,3</sup>. Neuroblastoma is a paediatric cancer that harbours few mutations and is instead driven by epigenetically deregulated transcription ...[more]

PMID: 34732890

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Project description:Biomaterials play an increasing role in clinical applications and regenerative medicine. Modern biomaterials should imitate the function of damaged tissue without triggering an immune response, initiate self-regeneration of the body and gradually degrade after implantation. The immune system is now well recognized to play a major role in influencing the biocompatibility of implanted medical devices. To develop a better understanding of the effects of biomaterials on the immune response, we have developed a highly sensitive novel test system capable of examining changes in the immune system by biomaterial. Here, we evaluate for the first time the immunopeptidome, a highly sensitive system that reflects cancer transformation, virus or drug influences and passes these changes directly to T cells, as a test system to examine the effects of contact with materials. Since monocytes are one of the first immune cells reacting to biomaterials, we have tested the influence of different materials - stainless steel, aluminum, zinc, high-density polyethylene, polyurethane films containing zinc diethyldithiocarbamate, copper, and zinc sulphate - on the monocytic THP-1 cell line. Material-associated peptides were identified after stimulation with all material types examined. The magnitude of induced changes in the immunopeptidome after the stimulation appears comparable to that of bacterial lipopolysaccharides (LPS). The source proteins of many detected peptides are associated with cytotoxicity, fibrosis, autoimmunity, inflammation and cellular stress. Considering all tested materials, it was found that the LPS-induced cytotoxicity-, inflammation- and cellular stress-associated HLA class I peptides were mainly induced by aluminum and HLA class II peptides mainly by stainless steel. These findings provide some of the first insights into the effects on the immunopeptidome by biomaterials. A more thorough understanding of these effects may enable the design of more biocompatible implant materials using in vitro models in future. This may be achieved through developing a deeper understanding of possible immune responses induced by biomaterials such as fibrosis, inflammation, cytotoxicity, and autoimmune reactions.