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Defining the immunophenotype within the clear cell renal cell carcinoma tumour microenvironment to guide immune checkpoint blockade

ABSTRACT: Defining the immunophenotype within the clear cell renal cell carcinoma tumour microenvironment to guide immune checkpoint blockade

PROVIDER: PRJEB60597 | ENA |

REPOSITORIES: ENA

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Defining the immunophenotype within the clear cell renal cell carcinoma tumour microenvironment to guide immune checkpoint blockade

Project description:We performed spatial transcriptome profiling (ST-seq) on nine fresh frozen tissue sections to understand the immunophenotypes; immune cell types, states and their spatial location within the clear cell renal cell carcinoma (ccRCC) tumour microenvironment (TME).

2023-08-16 | E-MTAB-12767 | biostudies-arrayexpress

HIF-1α and HIF-2α differently regulate tumour development, metabolism and inflammation of clear cell renal cell carcinoma in mice

Project description:Mutational inactivation of VHL is the earliest genetic event in the majority of ccRCCs, leading to activation of the HIF-1α and HIF-2α transcription factors. While correlative studies of human ccRCCs and functional studies using human ccRCC cell lines have implicated HIF-1α as an inhibitor and HIF-2α as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Using an autochthonous ccRCC model, we show genetically that Hif1a is necessary for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1α and HIF-2α are necessary for the clear cell phenotype. Transcriptomic and proteomic analyses revealed that HIF-1α regulates glycolysis while HIF-2α regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. Deficiency of HIF-2α increased CD8+ T cell infiltration and activation. These studies reveal different functions of HIF-1α and HIF-2α in ccRCC. SIGNIFICANCE The roles of HIF-1α and HIF-2α in ccRCC pathogenesis remain unclear. Using a mouse genetic approach we show that HIF-1α but not HIF-2α is important for tumour formation, contrary to predictions from studies of human ccRCC. We show that HIF-1α and HIF-2α transcriptionally regulate different aspects of metabolism and identify HIF-2α as a suppressor of immune cell infiltration and activation.

2020-07-02 | PXD016630 | Pride

An immunophenotype coupled transcriptomic atlas of human hematopoietic progenitors

Project description:An immunophenotype coupled transcriptomic atlas of human hematopoietic progenitors

| PRJNA1026952 | ENA

LSK immunophenotype hematopoietic stem cells in Dapp1 knockout mice

Project description:LSK immunophenotype hematopoietic stem cells in Dapp1 knockout mice

| PRJNA1161661 | ENA

HIF-1a and HIF-2a differently regulate tumour development, metabolism and inflammation of clear cell renal cell carcinoma in mice

Project description:Mutational inactivation of VHL is the earliest genetic event in the majority of clear cell renal cell carcinomas (ccRCC), leading to accumulation of the HIF-1alpha and HIF-2a transcription factors. While correlative studies of human ccRCC and functional studies using human ccRCC cell lines have implicated HIF-1a as an inhibitor and HIF-2a as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Using an autochthonous ccRCC model, we show genetically that Hif1a is essential for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1a and HIF-2a are required for the clear cell phenotype. Transcriptomic and proteomic analyses revealed that HIF-1alpha regulates glycolysis while HIF-2a regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. HIF-2a-deficient tumours were characterised by increased antigen presentation, interferon signalling and CD8+ T cell infiltration and activation. Single copy loss of HIF1A or high levels of HIF2A mRNA expression correlated with altered immune microenvironment in human ccRCC. These studies reveal an oncogenic role of HIF-1alpha in ccRCC initiation and suggest that alterations in the balance of HIF-1alpha and HIF-2a activities can affect different aspects of ccRCC biology and disease aggressiveness.

2020-05-22 | GSE150983 | GEO

LSK immunophenotype hematopoietic stem cells after irradiation at day 2

Project description:LSK immunophenotype hematopoietic stem cells after irradiation at day 2

| PRJNA1168177 | ENA

Single-cell RNA-seq identification of the cellular molecular characteristics of sporadic bilateral clear cell renal cell carcinoma

Project description:Bilateral renal cell carcinoma (RCC) is a rare type of this disease and includes familial bilateral and sporadic bilateral RCCs. Studying the cellular molecular characteristics of sporadic bilateral is important to provide a direct guide for clinical treatment. These cellular molecular characteristics can be expressed at the RNA level, especially at the single-cell RNA level. Single-cell RNA sequencing (scRNA-seq) was performed on bilateral clear cell RCC (ccRCC). A total of 3,575 and 3,568 high-quality single-cell transcriptome data were captured from the left and right tumour tissues, respectively. Gene characteristics were identified by comparing left and right tumours at the scRNA level. This work presented the complex cellular environment of bilateral ccRCC by scRNA-seq. Single-cell transcriptome analysis revealed high similarity in gene expression among most cell types of bilateral RCCs but significant differences in gene expression among different site tumour cells. Additionally, the potential biological function of different tumour cell types was determined by gene ontology (GO) analysis. The transcriptome characteristics of tumour tissues in different locations at the single-cell transcriptome level were revealed through the scRNA-seq of bilateral sporadic ccRCC. This work provides new insights into the diagnosis and treatment of bilateral RCC.

2021-05-05 | GSE171306 | GEO

Expression data from tumour celllines and non-tumour cells.

Project description:Expression data from tumour celllines and non-tumour cells.

| PRJNA523006 | ENA

Detecting circulating tumour DNA from gestational trophoblastic tumour using common SNPs

Project description:Gestational tumour diagnosis using circulating tumour DNA

| PRJEB49976 | ENA

Mutational heterogeneity between different regional tumour grades of clear cell renal cell carcinoma

Project description:Mutational heterogeneity between different regional tumour grades of clear cell renal cell carcinoma by exome sequencing and targeted SPET sequencing

| PRJEB37556 | ENA

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