Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting TNK2 reverses the immunosuppressive tumor microenvironment and synergizes with immunochemotherapy in pancreatic cancer

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Pancreatic Ductal Cell, Cell Culture

DISEASE(S): Carcinoma

SUBMITTER: chao wu

LAB HEAD: Jihui Hao

PROVIDER: PXD055503 | Pride | 2025-10-11

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Membrane_protein_peptides_of_KPC_TNK2.raw	Raw
	Membrane_protein_peptides_of_KPC_Vector.raw	Raw
	diffEXp.xlsx	Xlsx

Items per page:

1 - 3 of 3

Similar Datasets

Abnormal expression of glucose transporter-1 are a driver of early relapse in follicular lymphoma

Project description:FL patients with high GLUT1 levels are at increased risk for early relapse and show only limited responses to PI3K inhibitors. The development of new therapies requires an understanding of the changes in their tumor immune microenvironment (TIME). Using novel IMC and proteomics techniques, we comprehensively identified distinguishing features in the TIME as a function of GLUT1 levels. Bioinformatics analyses identified a crosstalk between GLUT1 and TIME in tumor development and suggest that FL patients expressing high GLUT1 may benefit from metabolic-modulating therapies to prevent early relapse.

2023-03-11 | PXD031257 | Pride

MicroRNA expression data from H1299 cells

Project description:We explored the biological effects of AGO2 downregulation on the expression of miRNAs in human NSCLC cells. Using AGO2 siRNA as a positive control, we overexpressed miR-138 in H1299 cells to observe changes in the miRNA profile using an miRNA microarray assay. Total RNAs were extracted from H1299 cells transfected with NC, AGO2 siRNA or miR-138 for 48h. Their microRNAs expression profiles were investigated using LCSciences Human miRNA Array platform (LCSciences, Houston, TX; Sanger mirBase Release 19.0).

2015-06-05 | E-GEOD-69561 | biostudies-arrayexpress

Single cell RNA sequencing of paired non small cell lung carcinoma tissue and peripheral blood from 5 donors

Project description:The immunosuppressive tumour microenvironment constitutes a significant hurdle to immune checkpoint inhibitors response. Both soluble factors and specialised immune cells such as regulatory T cells (TReg) are key components of active intratumoural immunosuppression. Previous studies have shown that Inducible Co-Stimulatory receptor (ICOS) can be highly expressed in the tumour microenvironment, especially on immunosuppressive TReg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we performed immune profiling of samples from paired tumour and peripheral blood of 5 patients with non-small cell lung cancer (NSCLC). We found Icos mRNA expression in NSCLC samples was higher in TRegs than in other T cell subsets and higher in the TME than in the periphery with the expression pattern in both compartments following the general trend of: TReg > CD4non-TReg > CD8 > Other.

2020-09-01 | E-MTAB-9451 | biostudies-arrayexpress

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and snf[148] ovary Transcriptomes

Project description:Comparison of wild type and tumorous ovaries reveals that tumors inappropriately express a large number of testis genes mRNA profiles of ovaries from 0-24 hour virgin wild type (WT) and 3 day old snf[148] females were generated by deep sequencing, in duplicate, using Illumina HiSeq 2500.

2015-02-17 | E-GEOD-65932 | biostudies-arrayexpress

RNA-seq of pancreatic mouse tumor cell lines

Project description:KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) is highly immunosuppressive and resistant to targeted therapies, immune checkpoint blockade and engineered T cells. In this study, we performed a systematic high throughput combinatorial drug screen and identified a synergistic interaction between the MEK inhibitor trametinib and the multi-kinase inhibitor nintedanib. Using bulk and single-cell RNA sequencing and immunophenotyping, we show that the combination therapy reprograms the immunosuppressive microenvironment and primes cytotoxic and memory T cells to infiltrate the tumors, thereby sensitizing mesenchymal PDAC to PD-L1 inhibition.

2021-11-29 | E-MTAB-11187 | biostudies-arrayexpress

Single cell RNA-seq of pancreatic mouse tumors upon treatment

Project description:KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) is highly immunosuppressive and resistant to targeted therapies, immune checkpoint blockade and engineered T cells. In this study, we performed a systematic high throughput combinatorial drug screen and identified a synergistic interaction between the MEK inhibitor trametinib and the multi- kinase inhibitor nintedanib. Using single cell RNA sequencing and immunophenotyping, we show that the combination therapy reprograms the immunosuppressive microenvironment and primes cytotoxic and memory T cells to infiltrate the tumors, thereby sensitizing mesenchymal PDAC to PD-L1 inhibition.

2021-11-13 | E-MTAB-9954 | biostudies-arrayexpress

Global expression analysis identified a preferentially NGF-induced transcriptional program regulated by sustained MEK/ERK and AP-1 activation during PC12 differentiation.

Project description:Neuronal differentiation of PC12 cells in response to NGF is a prototypical model in which signal duration determines a biological response. Sustained ERK activity induced by NGF, as compared to transient activity induced by EGF, is critical to the differentiation of these cells. To characterize the transcriptional program activated preferentially by NGF, we compared global gene expression profiles between cells treated with NGF and EGF for 2-4 hrs, when sustained ERK signaling in response to NGF is most distinct from the transient signal elicited by EGF. This analysis identified 69 genes that were preferentially upregulated in response to NGF. PC12 cells that were starved in low serum media for 24 hrs were treated with NGF (50ng/mL) or EGF (25ng/mL) for 2 or 4 hrs, or left untreated. Total RNA for 3 independent biological replicates was extracted and subjected to Affymetrix Rat Gene 1.0ST Arrays. The 69 genes that were preferentially upregulated by NGF compared to EGF met the following criteria: NGF/No treatment log2> 1, FDR p value< 0.01 and NGF/EGF log2> 0.75, FDR p value< 0.01.

2011-11-13 | E-GEOD-33639 | biostudies-arrayexpress

Rhizogenic Agrobacterium protein RolB interacts with the TOPLESS and NINJA repressor proteins to reprogram plant jasmonate signaling.

Project description:RNA sequencing was performed to compare the gene expression in tomato roots upon infection with the wild-type rhizogenic Agrobacterium K599 strain, the rolB∆ mutant strain and the rolB∆ strain with the constructs expressing either the native rolB oncogene or the rolBmEAR2 mutant.

2022-12-05 | E-MTAB-12405 | biostudies-arrayexpress

Differences in proteins between normal and asthmatic mice and effects of knockout TL1A on asthmatic mice

Project description:Asthma, a heterogeneous disease, is characterized by chronic inflammation, epithelial–mesenchymal transformation (EMT), and airway remodeling. After immune system activation, macrophages, T cells, and other cells gather and secrete various factors, such as interleukin-1β, 4, 5, 10, 13, and TNF-a, which break the anti-inflammatory balance and aggravate the progression of asthma. TNF-a, a member of the TNF superfamily, has promising future in the pathophysiological progress of autoimmune diseases and the development and application of related drugs. However, the mechanisms of TNF-a in mucus secretion, airway hyperreactivity, and airway remodeling of human asthma remains unclear. Tumor necrosis factor-like cytokine 1A is a type II transmembrane protein with a stable trimer structure similar to TNF-a. Migone et al. first uncovered the presence of TL1A as a membrane-bound protein (mTL1A) or a soluble protein (sTL1A) from mTL1A cleaved by an underlying enzyme. DR3 is a type I membrane protein that contains a death domain in the cytoplasmic region and remains highly homologous with other TNFRSF members. Interestingly, Evangelos et al. found that TNF-a-stimulated human lung myofibroblasts significantly increase TL1A expression and collagen production. Our study will identify the specific role of TNF-a-stimulated mTL1A/DR3 or sTL1A/DR3 axis in the EMT of asthma model.

2022-05-20 | PXD031079 | Pride

Expression data from H1299 cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-06-05 | E-GEOD-69563 | biostudies-arrayexpress