Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model

Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Cancers
Volume: 11
Number: 1
Page Range: p. 32
Date: 2018
Divisions: Liver Enzymes in Metabolism and Inflammation
Depositing User: General Admin
Identification Number: 10.3390/cancers11010032
ISSN: 2072-6694
Date Deposited: 21 Dec 2020 05:52

Ovarian cancers (OCs) are the most lethal gynaecological malignancy, with high levels of relapse and acquired chemo-resistance. Whilst the tumour⁻immune nexus controls both cancer progression and regression, the lack of an appropriate system to accurately model tumour stage and immune status has hampered the validation of clinically relevant immunotherapies and therapeutic vaccines to date. To address this need, we stably integrated the near-infrared phytochrome iRFP720 at the ROSA26 genomic locus of ID8 mouse OC cells. Intrabursal ovarian implantation into C57BL/6 mice, followed by regular, non-invasive fluorescence imaging, permitted the direct visualization of tumour mass and distribution over the course of progression. Four distinct phases of tumour growth and dissemination were detectable over time that closely mimicked clinical OC progression. Progression-related changes in immune cells also paralleled typical immune profiles observed in human OCs. Specifically, we observed changes in both the CD8+ T cell effector (Teff):regulatory (Treg) ratio, as well as the dendritic cell (DC)-to-myeloid derived suppressor cell (MDSC) ratio over time across multiple immune cell compartments and in peritoneal ascites. Importantly, iRFP720 expression had no detectible influence over immune profiles. This new model permits non-invasive, longitudinal tumour monitoring whilst preserving host⁻tumour immune interactions, and allows for the pre-clinical assessment of immune profiles throughout disease progression as well as the direct visualization of therapeutic responses. This simple fluorescence-based approach provides a useful new tool for the validation of novel immuno-therapeutics against OC.

Keywords: ID8; T cell; iRFP; iRFP720; immune; ovarian cancer; syngeneic; tumour.

Wilson, Amy
Wilson, Kirsty
Bilandzic, Maree
Moffitt, Laura
Makanji, Ming
Gorrell, Mark
Oehler, Martin
Rainczuk, Adam
Stephens, Andrew
Plebanski, Magdalena
Last Modified: 21 Dec 2020 05:52

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