| 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
IFNgamma 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.
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