PXD055503-1

PXD055503 is an original dataset announced via ProteomeXchange.

Title	Targeting TNK2 reverses the immunosuppressive tumor microenvironment and synergizes with immunochemotherapy in pancreatic cancer
Description	In this study, we utilized spatial transcriptome analysis, genomic copy number variation mutation profiling, and single-cell sequencing to identify an abnormal overexpression of TNK2, which is inversely correlated with PDAC prognosis and the development of an immune-suppressive microenvironment. Previous research has hinted at TNK2's role in tumor progression and its correlation with patient survival in various cancers, yet its involvement in the PDAC immune microenvironment and resistance to immunotherapy remains unexplored. Our findings reveal that TNK2 overexpression influences the formation of an immunosuppressive microenvironment, as demonstrated by cell communication analysis and immune landscape profiling. Additionally, TNK2 phosphorylates and activates STAT5a at the Y694 site, resulting in the upregulation of immune checkpoint HVEM and the exhaustion of CD8+ T cells. Treatment with AIM100, which disrupts the TNK2-STAT5a-HVEM regulatory axis, markedly mitigates the immunosuppressive microenvironment and enhances sensitivity to PD-1 inhibitors and AG chemotherapy.
HostingRepository	PRIDE
AnnounceDate	2025-10-11
AnnouncementXML	Submission_2025-10-11_04:43:56.056.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	chao wu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ FT

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-03 02:06:25	ID requested
⏵ 1	2025-10-11 04:43:56	announced

Dataset with its publication pending

ProteomeXchange project tag: Cancer (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: immunosuppressive tumor microenvironment, immunotherapy resistance,Pancreatic ductal adenocarcinoma, TNK2

Jihui Hao
contact affiliation	Tianjin Medical University Cancer Institute and Hospital
contact email	haojihui@tjmuch.com
lab head
chao wu
contact affiliation	Tianjin Medical University Cancer Institute and Hospital
contact email	wuchaozhicheng@126.com
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/2025/10/PXD055503

PRIDE project URI

• PRIDE
  1. PXD055503
     1. Label: PRIDE project
     2. Name: Targeting TNK2 reverses the immunosuppressive tumor microenvironment and synergizes with immunochemotherapy in pancreatic cancer