⮝ Full datasets listing
PXD075012
PXD075012 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Ceramide Disrupts TM9SF2-PGK1 Axis to Redirect PD-L1 Trafficking and Enhance Antitumor Immunity |
| Description | The programmed cell death protein 1 (PD-1) / programmed death-ligand 1 (PD-L1) axis represents a cornerstone of cancer immunotherapy, yet the dynamic shuttling of PD-L1 between endosomal recycling and lysosomal degradation routes limits durable responses. Using a CRISPR screen targeting glycosphingolipid metabolism, we identify transmembrane 9 superfamily member 2 (TM9SF2) as a key regulator of PD-L1 levels. TM9SF2 orchestrates a dual mechanism: it recruits phosphoglycerate kinase 1 (PGK1) to promote PD-L1 recycling to the plasma membrane while dismantling the huntingtin-interacting protein 1-related protein (HIP1R)-mediated lysosomal degradation pathway. Genetic or pharmacological disruption of the TM9SF2-PGK1 complex depletes PD-L1 levels and boosts antitumor immunity. Further, the endogenous ceramide species Cer(d18:1/26:0) destabilizes this complex, triggering PD-L1 lysosomal destruction and potentiating antitumor immunity. These findings delineate a ceramide-gated sorting mechanism within the endosomal network, revealing a druggable metabolic switch to disrupt immune evasion and amplify checkpoint blockade efficacy. |
| HostingRepository | iProX |
| AnnounceDate | 2026-02-27 |
| AnnouncementXML | Submission_2026-02-27_18:59:26.397.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Mengmeng Wang |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-02-27 18:59:11 | ID requested | |
| ⏵ 1 | 2026-02-27 18:59:26 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: PD-L1, endosome, TM9SF2, anti-tumor, ceramide, immunotherapy |
Contact List
| Ting Dong | |
|---|---|
| contact affiliation | Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College |
| contact email | tingdong2025@pumc.edu.cn |
| lab head | |
| Mengmeng Wang | |
| contact affiliation | Shandong University |
| contact email | wmm20201101@163.com |
| dataset submitter | |
Full Dataset Link List
| iProX dataset URI |
