PXD039710

PXD039710 is an original dataset announced via ProteomeXchange.

Title	The CD58:CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity
Description	The cell-autonomous balance of immune-inhibitory and -stimulatory signals is a critical process in cancer immune evasion. Using patient-derived co-cultures, humanized mouse models, and single cell RNA-sequencing of patient melanomas biopsied before and on immune checkpoint blockade, we find that intact cancer-cell-intrinsic expression of CD58 and ligation to CD2 is required for anti-tumor immunity and is predictive of treatment response. Defects in this axis promote immune evasion through diminished T cell activation, impaired intratumoral T cell infiltration and proliferation, and concurrently increased PD-L1 protein stabilization. Through CRISPR-Cas9 and proteomics screens, we identify and validate CMTM6 as critical for CD58 maintenance and upregulation of PD-L1 upon CD58 loss. Competition by CD58 and PD-L1 for CMTM6 (via both extracellular loop domains) determines their rate of endosomal recycling over lysosomal degradation. Overall, we describe an underappreciated yet critical axis of cancer immunity and provide a molecular basis for how cancer cells balance immune inhibitory and stimulatory cues.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:01:56.752.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Patricia Ho
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-27 10:51:32	ID requested
1	2023-07-06 06:14:12	announced
⏵ 2	2023-11-14 09:02:03	announced	2023-11-14: Updated project metadata.

Ho P, Melms JC, Rogava M, Frangieh CJ, Po, ź, niak J, Shah SB, Walsh Z, Kyrysyuk O, Amin AD, Caprio L, Fullerton BT, Soni RK, Ager CR, Biermann J, Wang Y, Khosravi-Maharlooei M, Zanetti G, Mu M, Fatima H, Moore EK, Vasan N, Bakhoum SF, Reiner SL, Bernatchez C, Sykes M, Mace EM, Wucherpfennig KW, Schadendorf D, Bechter O, Shah P, Schwartz GK, Marine JC, Izar B, The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity. Cancer Cell, 41(7):1207-1221.e12(2023) [pubmed]

submitter keyword: Human, CD58,Melanoma

Benjamin Izar
contact affiliation	Department of Medicine, Columbia University
contact email	bi2175@cumc.columbia.edu
lab head
Patricia Ho
contact affiliation	Columbia University
contact email	ph2565@cumc.columbia.edu
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/2023/07/PXD039710

PRIDE project URI

• PRIDE
  1. PXD039710
     1. Label: PRIDE project
     2. Name: The CD58:CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity