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

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

PROVIDER: PRJEB42702 | ENA |

REPOSITORIES: ENA

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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

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: IT_and_cont_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 after treatment with immunotherapy.

2022-08-02 | GSE210051 | GEO

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: IT_and_cont_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 after treatment with immunotherapy.

2022-08-02 | GSE210050 | GEO

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: CD8_NK_depletion_4T1_BC5000_rpt]

2022-08-02 | GSE210049 | GEO

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: All_EMT6_BC5000]

Project description:To investigate immunoediting at the primary tumour, we used DNA barcoding combined with NGS. By stably integrating EMT6 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 after treatment with immunotherapy.

2022-08-02 | GSE210047 | GEO

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: CD8 NK depletion 4T1 BC5000]

2022-08-02 | GSE210048 | GEO

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 [DNA barcodes: WT_nude_and_NSG_4T1_BC250000]

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]

2022-08-02 | GSE210052 | GEO

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

Project description: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.

2022-08-02 | GSE210055 | GEO

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