PXD059837

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

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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