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

Louise A. Baldwin, Nenad Bartonicek, Jessica Yang, Sunny Z. Wu, Niantao Deng, Daniel L. Roden, Chia-Ling Chan, Ghamdan Al-Eryani, Damien J. Zanker, Belinda S. Parker, Alexander Swarbrick () and Simon Junankar
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Louise A. Baldwin: Garvan Institute of Medical Research
Nenad Bartonicek: Garvan Institute of Medical Research
Jessica Yang: Garvan Institute of Medical Research
Sunny Z. Wu: Garvan Institute of Medical Research
Niantao Deng: Garvan Institute of Medical Research
Daniel L. Roden: Garvan Institute of Medical Research
Chia-Ling Chan: Garvan Institute of Medical Research
Ghamdan Al-Eryani: Garvan Institute of Medical Research
Damien J. Zanker: University of Melbourne
Belinda S. Parker: University of Melbourne
Alexander Swarbrick: Garvan Institute of Medical Research
Simon Junankar: Garvan Institute of Medical Research

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-34041-x

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