PXD048903

PXD048903 is an original dataset announced via ProteomeXchange.

Title	Targeting PILRα, an immune checkpoint mediating T cell suppression, for cancer immunotherapy
Description	One of the most successful therapies in cancer treatment involves immune checkpoint blockade using the anti-programmed death-1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) antibody, which targets the interaction between tumors and T cells. However, the overall response rate is < 30% in patients with cancer. Therefore, there is an urgent need to identify additional immune checkpoints that can modulate T-cell function. In this study, we identified the tumor cell-expressed paired Ig-like type 2 receptor α (PILRα) as an immune suppressor that targets T cells, using a high-throughput screening approach. PILRα suppresses T-cell activation, proliferation, and effector function in both cultured cells and mouse xenograft and allograft models. It specifically targets CD99, a T cell surface antigen, to suppress the ZAP70/NFAT/IL2/JAK/STAT signaling in T cells. The cluster of O-glycosylated serine (Ser)/threonine (Thr) residues within the stalk region plays a critical role in PILRα–CD99 interactions, thereby influencing the immunosuppressive function of PILRα. Blocking interactions between PILRα and CD99 using an anti-PILRα antibody that targets the stalk region potently enhances T cell antitumor immunity and suppresses tumor growth. Additionally, when combined anti-PILRα with anti-PD-1 antibodies, synergistic effects on tumor suppression were observed. Notably, PILRα is highly expressed in various human cancers, and its expression levels serve as a predictive marker for poor prognosis in patients with cancer. Taken together, our results unveil PILRα as an immune checkpoint and highlight the promising therapeutic potential of targeting PILRα in clinical cancer immunotherapy.
HostingRepository	iProX
AnnounceDate	2024-01-25
AnnouncementXML	Submission_2025-03-13_18:36:39.737.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yaohui He
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-25 18:15:55	ID requested
⏵ 1	2025-03-13 18:36:40	announced

Dataset with its publication pending

submitter keyword: PILRα, immune checkpoint, T-cell, CD99, cancer immunotherapy

Wen Liu
contact affiliation	Xiamen University
contact email	w2liu@xmu.edu.cn
lab head
Yaohui He
contact affiliation	Xiamen University
contact email	yhhe@xmu.edu.cn
dataset submitter

iProX dataset URI