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Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma [spatial transcriptomics]

ABSTRACT: Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma [spatial transcriptomics]

PROVIDER: PRJNA863569 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20708363_1.fastq.gz	Fastqsanger.gz
	SRR20708363_2.fastq.gz	Fastqsanger.gz
	SRR20708364_1.fastq.gz	Fastqsanger.gz
	SRR20708364_2.fastq.gz	Fastqsanger.gz

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Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma

Project description:Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma

| PRJNA863561 | ENA

Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma [scRNA-seq]

Project description:Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma [scRNA-seq]

| PRJNA863568 | ENA

Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma [scRNA-seq]

Project description:Immune checkpoint inhibitors (ICI) represent the cornerstone for treatment of patients with metastatic clear-cell renal cell carcinoma (ccRCC). Despite a favorable response for a subset of patients, others experience primary progressive disease highlighting the need to precisely understand plasticity of cancer cells and their crosstalk with the microenvironment to better predict therapeutic response and personalize treatment. Single-cell RNA sequencing of ccRCC at different disease stages and normal adjacent tissue (NAT) from patients identified 46 cell populations, including 5 tumor subpopulations, characterized by distinct transcriptional signatures representing an epithelial to mesenchymal transition gradient and a novel inflamed state. Deconvolution of the tumor and microenvironment signatures in public datasets and in data from the BIONIKK clinical trial (NCT02960906) revealed a strong correlation between mesenchymal-like ccRCC cells and myofibroblastic cancer-associated fibroblasts (myCAFs), which are both enriched in metastases and correlate with poor patient survival. Spatial transcriptomics and multiplex immune staining uncovered spatial proximity of mesenchymal-like ccRCC cells and myCAFs at the tumor-NAT interface. Moreover, enrichment in myCAFs was associated with primary resistance to ICI therapy in the BIONIKK clinical trial. This data highlights the epithelial-mesenchymal plasticity of ccRCC cancer cells and their relationship with myCAFs, a critical component of the microenvironment associated with poor outcome and ICI resistance.

2023-06-26 | GSE210038 | GEO

Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma [spatial transcriptomics]

2023-06-26 | GSE210041 | GEO

Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-26 | GSE210042 | GEO

EMILIN2 is associated with prognosis and immunotherapy in clear cell renal cell carcinoma.

Project description:Background: EMILIN2 is a platelet-associated elastin that regulates angiogenesis. It has recently been found to play an essential role in various tumors. Nevertheless, the mechanism of action of EMILIN2 in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: Samples from 33 cancers were obtained from UCSC Xena and The Cancer Genome Atlas (TCGA) database. The relationship between EMILIN2 expression and the clinicopathological characteristics and immune infiltration of ccRCC was investigated. Nonnegative matrix factorization (NMF) was used to classify ccRCC patients. A multigene risk prediction model of ccRCC was constructed using LASSO regression and multivariate regression analysis. A nomogram survival probability prediction map and calibration curve were constructed based on clinical information. Results: EMILIN2 is significantly overexpressed in ccRCC, a phenomenon that is associated with poor prognosis. Meanwhile, EMILIN2 expression is closely related to tumor immune infiltration in ccRCC. Patients with clear cell renal cell carcinoma were divided into two subtypes using NMF, with subtype 2 showed poor prognosis. Next, we established a risk score model for ccRCC based on the common differentially expressed genes (DEGs) between subtypes and groups based on EMILIN2 expression. The results indicated poor prognosis in the high-risk group in the training set and were confirmed in the validation set. Conclusion: Our findings suggest that EMILIN2 expression is closely associated with immune infiltration in ccRCC. EMILIN2 expression is negatively correlated with the prognosis of ccRCC patients. Here, we developed a tool that could predict the prognosis of ccRCC patients.

| S-EPMC9760906 | biostudies-literature

Prrx1 is a Master Transcription Factor of myofibroblastic Cancer-Associated Fibroblasts

Project description:Prrx1 is a Master Transcription Factor of myofibroblastic Cancer-Associated Fibroblasts

| PRJNA717759 | ENA

Emerging Immunotherapy Approaches for Advanced Clear Cell Renal Cell Carcinoma.

Project description:The most common subtype of renal cell carcinoma is clear cell renal cell carcinoma (ccRCC). While localized ccRCC can be cured with surgery, metastatic disease has a poor prognosis. Recently, immunotherapy has emerged as a promising approach for advanced ccRCC. This review provides a comprehensive overview of the evolving immunotherapeutic landscape for metastatic ccRCC. Immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 and CTLA-4 inhibitors have demonstrated clinical efficacy as monotherapies and in combination regimens. Combination immunotherapies pairing ICIs with antiangiogenic agents, other immunomodulators, or novel therapeutic platforms such as bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapy are areas of active research. Beyond the checkpoint blockade, additional modalities including therapeutic vaccines, cytokines, and oncolytic viruses are also being explored for ccRCC. This review discusses the mechanisms, major clinical trials, challenges, and future directions for these emerging immunotherapies. While current strategies have shown promise in improving patient outcomes, continued research is critical for expanding and optimizing immunotherapy approaches for advanced ccRCC. Realizing the full potential of immunotherapy will require elucidating mechanisms of response and resistance, developing predictive biomarkers, and rationally designing combination therapeutic regimens tailored to individual patients. Advances in immunotherapy carry immense promise for transforming the management of metastatic ccRCC.

| S-EPMC10777977 | biostudies-literature

Senescent and myofibroblastic cancer-associated fibroblasts share a contractile phenotype regulated by NOX4 generation of reactive oxygen species in the tumour microenvironment

Project description:Cancer associated fibroblasts characterized by an myofibroblastic phenotype play a major role in the tumour microenvironment, being associated with poor prognosis. We found that this cell population is made in part by senescent fibroblasts in vivo. As senescent fibroblasts and myofibroblasts have been shown to share similar tumour promoting functions in vitro we compared the transcriptosomes of these two fibroblast types and performed RNA-seq of human foetal foreskin fibroblasts 2 (HFFF2) treated with 2ng/ml TGF-beta-1 to induce myofibroblast differentiation or 10Gy gamma irradiation to induce senescence. We isolated RNA 7 days upon this treatments changing the medium 3 days before the RNA extraction. A series of SAM alignment files (named after the sample names, for simplicity) are available under http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3101/files/ .

2017-06-01 | E-MTAB-3101 | biostudies-arrayexpress

The role of immunotherapy in non-clear cell renal cell carcinoma.

Project description:The category of non-clear cell renal cell carcinoma (nccRCC) includes several clinically, histologically, and molecularly diverse entities. Traditionally, they comprise type 1 and type 2 papillary, chromophobe, unclassified, and other histologies (medullary, collecting duct carcinoma, and translocation-associated). Molecular knowledge has allowed the identification of some other specific subtypes, such as fumarate hydratase-deficient renal cell carcinoma (RCC) or succinate dehydrogenase-associated RCC. In addition, it has recognized some alterations with a possible predictive role, e.g., MET proto-oncogene receptor tyrosine kinase (MET) alterations in papillary tumors. Standard therapies for the management of advanced clear cell RCC (ccRCC), i.e., vascular endothelial growth factor receptor (VEGFR) pathway inhibitors and mammalian target of rapamycin inhibitors, have shown poorer results in nccRCC patients. Therefore, there is a need to improve the efficacy of the treatment for advanced nccRCC. Immunotherapy, especially immune checkpoint inhibitors (ICIs) targeting programmed death 1/programmed death ligand 1 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4), has demonstrated a significant survival benefit in several malignant neoplasias, including ccRCC, with a proportion of patients achieving long survival. The combinations of ICI or ICI + VEGFR tyrosine kinase inhibitors (TKIs) are the standard of care in advanced ccRCC. Unfortunately, major pivotal trials did not include specific nccRCC populations. In recent years, several studies have retrospectively or prospectively evaluated ICIs alone or in combination with another ICI or with TKIs in nccRCC patients. In this article, we review data from available trials in order to elucidate clinical and molecular profiles that could benefit from immunotherapy approaches.

| S-EPMC9936973 | biostudies-literature

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