PXD050084

PXD050084 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-23 07:01:01	ID requested
⏵ 1	2024-10-17 02:37:11	announced

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]

submitter keyword: bottom up proteomics, proximity labelling,Cancer

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD050084

PRIDE project URI

• PRIDE
  1. PXD050084
     1. Label: PRIDE project
     2. Name: LRIG1 engages ligand VISTA and impairs tumor-specific CD8+ T cell responses