MassIVE MSV000096571

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Pan-cancer N-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as a therapeutic target for head and neck cancers

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Description

Here, we employed N-glycoproteomics to analyze 85 patient-derived xenografts (PDX), constructing Glyco PDXplorer - an in vivo pan-cancer atlas of cancer derived cell surface proteins. We developed a target discovery pipeline to prioritize proteins with favorable expression profiles for immunotherapeutic targeting and validated FAT2 as a head and neck squamous cancer (HNSC) enriched surface protein with limited expression in normal tissue. Functional studies revealed that FAT2 plays a crucial role in HNSC growth and adhesion through regulation of surface architecture and integrin-PI3K signaling. Chimeric antigen receptor (CAR) T cells targeting FAT2 demonstrated potent anti-tumor activity in HNSC models. This work lays the foundation for developing FAT2-targeted therapies and represents a pivotal resource to inform therapeutic target discovery for multiple cancers. [doi:10.25345/C5TB0Z68J] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Patient derived xenografts ; pan-cancer atlas ; N-glycoproteomics ; CAR-T immunotherapy ; FAT2 ; surfaceome ; targeted therapy ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Dr. Thomas Kislinger, Princess Margaret Cancer Centre, Canada
Submitting User: TKislinger
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