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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]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE210053 | GEO | 2022/08/02

REPOSITORIES: GEO

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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

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy [DNA barcodes: IT_and_cont_4T1_BC5000]

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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]

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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.

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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.

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

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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.

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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

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Digital counting of nucleic acid molecules using random base molecular barcodes

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Digital RNA Sequencing Minimizes Sequence-Dependent Bias and Amplification Noise with Optimized Single Molecule Barcodes

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