PXD050084 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | LRIG1 engages ligand VISTA and impairs tumor-specific CD8+ T cell responses |
Description | Cancer immunotherapies boost antitumor immunity and improve the survival of cancer patients. V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an immune 20 checkpoint target but presents elusive signaling mechanisms. We report a novel VISTA binding partner, Leucine-Rich Repeats and Immunoglobulin Like Domains 1 (LRIG1), which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell-specific LRIG1 deletion developed superior antitumor T cell responses. Mechanistically, LRIG1-deficient tumor-specific CD8+ cytotoxic T cells (CTLs) exhibited longer 25 persistence due to improved expansion and survival and greater effector function. Sustained tumor control was also associated with a reduction of quiescent CTLs (TCF1+ CD62Lhi PD-1low) and a reciprocal increase in progenitor and memory-like CTLs (TCF1+ PD-1+). In human melanoma, an elevated LRIG1 expression on tumor-infiltrating CD8+ CTLs correlated with resistance to immunotherapies. Taken together, these results delineate the role of LRIG1 as an inhibitory 30 immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-17 |
AnnouncementXML | Submission_2024-10-17_02:37:10.733.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD050084 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Belinda Willard |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-02-23 07:01:01 | ID requested | |
⏵ 1 | 2024-10-17 02:37:11 | announced | |
Publication List
10.6019/PXD050084; |
10.1126/sciimmunol.adi7418; |
Ta HM, Roy D, Zhang K, Alban T, Juric I, Dong J, Parthasarathy PB, Patnaik S, Delaney E, Gilmour C, Zakeri A, Shukla N, Rupani A, Phoon YP, Liu C, Avril S, Gastman B, Chan T, Wang LL, T cell responses. Sci Immunol, 9(95):eadi7418(2024) [pubmed] |
Keyword List
submitter keyword: bottom up proteomics, proximity labelling,Cancer |
Contact List
Li Lily Wang |
contact affiliation | Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic; Cleveland, OH. |
contact email | wangl9@ccf.org |
lab head | |
Belinda Willard |
contact affiliation | Cleveland Clinic |
contact email | willarb@ccf.org |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD050084
- Label: PRIDE project
- Name: LRIG1 engages ligand VISTA and impairs tumor-specific CD8+ T cell responses