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Innate lymphoid-macrophage crosstalk promotes lung cancer regression in response to IL-12 therapy

Henry, Jake Yarren; (2019) Innate lymphoid-macrophage crosstalk promotes lung cancer regression in response to IL-12 therapy. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The ability of IL-12 to affect both innate and adaptive immunity positions this cytokine as a promising candidate to overcome the immunosuppressive microenvironment within tumours. Despite its potent activity in experimental models, the clinical use of IL 12 has been thwarted by its reported toxicity in human trials. Intranasal administration of an IL-12-coding lentivirus efficiently transduced alveolar macrophages in tumour-bearing mice, restricting IL-12 expression to the lung parenchyma and promoting rejection of established lung metastases. IL-12 stimulated IFNγ production by innate lymphoid cells (ILC), inducing the activation of interstitial macrophages, whose presence was essential for tumour eradication. These data demonstrates the potent anti tumour activity of local lentiviral IL-12 therapy against metastatic disease in the lung and the critical role played by the innate crosstalk established between ILCs and tissue resident phagocytes within the lung microenvironment.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Innate lymphoid-macrophage crosstalk promotes lung cancer regression in response to IL-12 therapy
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10084584
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