PXD059837-1

PXD059837 is an original dataset announced via ProteomeXchange.

Title	Targeting Pim2 Improves Effector Function and Longevity of CD8 T cells in Cancer Immunotherapy
Description	The Pim kinase family is critically involved in tumorigenesis, yet its function in primary T cells remains poorly understood. We previously reported that Pim2 negatively regulates T-cell responses to alloantigen. To investigate how Pim2 impacts anti-tumor immunity of CD8 T cells, we generated Pim2-/- strains bearing tumor-antigen-specific T cells and performed adoptive T-cell therapy (ACT) against established tumor. We found that Pim2 restricts effector differentiation and persistence of CD8 T cells. As a result, Pim2-/- CD8 T cells exhibited greater potency than WT cells in controlling tumor growth across various cancer models. Mechanistically, Pim2 phosphorylates and inhibits its downstream target Vprbp, a kinase that phosphorylates and stabilizes Ezh2. Consistently, Pim2 deficiency increased Ezh2 expression and H3K27 trimethylation in CD8 T cells. Elevated Ezh2 activity in Pim2-/- CD8 T cells supported progenitor-like/memory differentiation within lymphoid organs. Furthermore, Pim2 deficiency diminished autophagy in CD8 T cells, thereby promoting glycolytic metabolism to drive effector T-cell differentiation in the tumor microenvironment (TME). In human T cells, silencinge Pim2 increased cytokine production and effector differentiation. A Pim2-specific inhibitor improved murine T-cell immunity against melanoma and increased the activity of human melanoma-specific T cells and CD19 CAR-T cells. Taken together, the current work reveals novel and compelling evidence to support Pim2 as a promising therapeutic target for improving cancer immunotherapy through enhancing effector differentiation and persistence of T cells.
HostingRepository	PRIDE
AnnounceDate	2026-01-08
AnnouncementXML	Submission_2026-01-08_12:59:47.749.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-15 14:05:37	ID requested
⏵ 1	2026-01-08 12:59:48	announced

Dataset with its publication pending

submitter keyword: Pim2, T cells,Cancer, Immunotherapy

Xue-Zhong Yu
contact affiliation	Department of Microbiology & Immunology, 2the Cancer Center, Medical College of Wisconsin Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
contact email	xuyu@mcw.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.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/2026/01/PXD059837

PRIDE project URI

• PRIDE
  1. PXD059837
     1. Label: PRIDE project
     2. Name: Targeting Pim2 Improves Effector Function and Longevity of CD8 T cells in Cancer Immunotherapy