PXD039542

PXD039542 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	G9a/GLP inhibition during ex vivo lymphocyte expansion increases in vivo cytotoxicity of engineered TCR-T cells against hepatocellular carcinoma
Description	Engineered T cells transiently expressing tumor-targeting receptors are an attractive form of engineered T cell therapy as they carry no risk of insertional mutagenesis or long-term adverse side-effects. However, multiple rounds of treatment are often required, increasing patient discomfort and cost. To mitigate this, we sought to improve the antitumor activity of transient engineered T cells by screening a panel of small molecules targeting epigenetic regulators for their effect on T cell cytotoxicity. Using a model for engineered T cells targetting hepatocellular carcinoma, we find that short-term inhibition of G9a/GLP increases T cell antitumor activity in in vitro models and an orthotopic mouse model. G9a/GLP inhibition increases granzyme expression without terminal T cell differentiation or exhaustion and results in specific changes in expression of genes and proteins involved in pro-inflammatory pathways, T cell activation and cytotoxicity.
HostingRepository	jPOST
AnnounceDate	2023-01-19
AnnouncementXML	Submission_2023-04-02_20:16:36.681.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Radoslaw Sobota
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide; S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; deamidated L-asparagine; deamidated L-glutamine; unknown modification; unknown modification
Instrument	Orbitrap Fusion

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-18 08:44:21	ID requested
1	2023-01-18 08:44:58	announced
⏵ 2	2023-04-02 20:16:37	announced	2023-04-03: Updated PubMed.

Publication List

Lam MSY, Reales-Calderon JA, Ow JR, Aw JJY, Tan D, Vijayakumar R, Ceccarello E, Tabaglio T, Lim YT, Chien WL, Lai F, Tanoto AT, Chen Q, Sobota RM, Adriani G, Bertoletti A, Guccione E, Pavesi A, G9a/GLP inhibition during ex vivo lymphocyte expansion increases in vivo cytotoxicity of engineered T cells against hepatocellular carcinoma. Nat Commun, 14(1):563(2023) [pubmed]

Lam MSY, Reales-Calderon JA, Ow JR, Aw JJY, Tan D, Vijayakumar R, Ceccarello E, Tabaglio T, Lim YT, Chien WL, Lai F, Tanoto AT, Chen Q, Sobota RM, Adriani G, Bertoletti A, Guccione E, Pavesi A, G9a/GLP inhibition during ex vivo lymphocyte expansion increases in vivo cytotoxicity of engineered T cells against hepatocellular carcinoma. Nat Commun, 14(1):563(2023) [pubmed]

Keyword List

submitter keyword: G9a, hepatocellular carcinoma, immunotherapy, T-cells

submitter keyword: G9a, hepatocellular carcinoma, immunotherapy, T-cells

Contact List

Andrea Pavesi
lab head
Radoslaw Sobota
contact affiliation	IMCB A-STAR Singapore
dataset submitter

Full Dataset Link List

jPOST dataset URI
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jPOST dataset URI

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.jpostdb.org/JPST001995/