Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [WGS of target clones]

ABSTRACT: By using DNA barcoding to trace individual cancer cells from the 4T1 murine model of cancer, we were able to identify two cancer cell clones that were highly immune evasive and resistant to immune destruction both by the endogenous immune system and when treating with immunotherapy. We isolated these clones (IE1 and IE2) from the bulk parental population for further characterisation. We wondered if copy number variations could explain the phenotype we observed, so we carried out WGS to investigate this.

ORGANISM(S): Mus musculus

PROVIDER: GSE210055 | GEO | 2022/08/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [Bulk RNAseq]

Project description:To investigate immunoediting at the primary tumour, we used DNA barcoding combined with NGS to identify individual cancer cells wthin the 4T1 murine model of cancer. We isolated two highly immune evasive clones from the parental population and carried out buk RNA sequencing

2022-08-02 | GSE210054 | GEO

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy

Project description:Cancers evade the immune system in order to grow or metastasise through the process of cancer immunoediting. While checkpoint inhibitor therapy has been effective for reactivating tumour immunity in some cancers, many solid cancers, including breast cancer, remain largely non-responsive. Understanding the way non-responsive cancers evolve to evade immunity, what resistance pathways are activated and whether this occurs at the clonal level will improve immunotherapeutic design. We tracked cancer cell clones during the immunoediting process and determined clonal transcriptional profiles that allow immune evasion in murine mammary tumour growth in response to immunotherapy with anti-PD1 and anti-CTLA4. Clonal diversity was significantly restricted by immunotherapy treatment at both the primary and metastatic sites. These findings demonstrate that immunoediting selects for pre-existing breast cancer cell populations, that immunoediting is not a static process and is ongoing during metastasis and immunotherapy treatment. Isolation of immunotherapy resistant clones revealed unique and overlapping transcriptional signatures. The overlapping gene signature was predictive of poor survival in basal-like breast cancer patient cohorts. Some of these overlapping genes have existing small molecules which can be used to potentially improve immunotherapy response.

2021-09-01 | E-MTAB-10027 | biostudies-arrayexpress

miRNA-mediated targeting of human cytomegalovirus reveals biological host and viral targets of IE2

Project description:We introduce target sites for the microRNA (miRNA) miR-142 into the 3’-untranslated region of the human cytomegalovirus (HCMV) IE2 to study the transcriptional effect of IE2 knock-down on both viral and host genes in cells that express miR-142. When comparing transcriptional data from miR-142 expressing macrophages infected with HCMV to macrophages infected with IE2-miR-142 targeted HCMV, we see a knock-down of IE2 and differential regulation of predicted viral targets of IE2 including IE1, vIL-10 and US29. We then generated fibroblasts expressing miR-142 to study the knock-down of IE2 in a different cellular system and find drastic differences in loss of IE2 on the host transcriptional profile in the two different cell types.

2017-12-28 | GSE107680 | GEO

Staphylococcus aureus

Project description:S. aureus IE1 and IE2 sequencing

| PRJNA898597 | ENA

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and immunotherapy response.

Project description:Cancers evade the immune system through the process of cancer immunoediting. While immune checkpoint inhibitors are effective for reactivating tumour immunity in some cancer types, many other solid cancers, including breast cancer, remain largely non-responsive. Understanding how non-responsive cancers evade immunity and whether this occurs at the clonal level will improve immunotherapeutic design. Here we use DNA barcoding to track murine mammary cancer cell clones during immunoediting and determine clonal transcriptional profiles that allow immune evasion following anti-PD1 plus anti-CTLA4 immunotherapy. Clonal diversity is significantly restricted by immunotherapy treatment in both primary tumours and metastases, demonstrating selection for pre-existing breast cancer cell populations and ongoing immunoediting during metastasis and treatment. Immunotherapy resistant clones express a common gene signature associated with poor survival of basal-like breast cancer patient cohorts. At least one of these genes has an existing small molecule that can potentially be used to improve immunotherapy response.

| S-EPMC9640547 | biostudies-literature

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: WT_nude_and_NSG_4T1_BC250000]

Project description:To investigate immunoediting at the primary tumour, we used DNA barcoding combined with NGS. By stably integrating 4T1 murine cancer cell line with 250000 unique DNA barcodes (1 barcode per cell), we can trace how barcode (and therefore subclonal) diversity changes over time and in the presence of the endogenous immune system, compared to immunocompromised mice.

2022-08-02 | GSE210053 | GEO

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: WT_nude_and_NSG_4T1_BC5000]

Project description:To investigate immunoediting at the primary tumour, we used DNA barcoding combined with NGS. By stably integrating 4T1 murine cancer cell line with 5000 unique DNA barcodes (1 barcode per cell), we can trace how barcode (and therefore subclonal) diversity changes over time and in reponse to the endogenous immune system in immunocompetent mice compared to immunocompromised mice.

2022-08-02 | GSE210052 | GEO

Cytomegalovirus promotes maintenance and growth of glioblastoma stem cells [Human gene expression]

Project description:Primary human GBM stem like cells were infected with HCMV TR strain (MOI=1) and treated with IE siRNA (a combination of oligos targeting IE1 and IE2 HCMV genes) 72 hours following siRNA treatment, RNA was harvested using Qiagen and divided equally for profiling using Affymetrix arrays and HCMV arrays.

2015-08-13 | GSE56715 | GEO

Cytomegalovirus promotes maintenance and growth of glioblastoma stem cells [HCMV gene expression]

2015-08-13 | GSE56750 | GEO

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: IT_and_cont_4T1_BC250000]

2022-08-02 | GSE210051 | GEO