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

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 ham...

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Autores principales: Wilson, Amy L., Wilson, Kirsty L., Bilandzic, Maree, Moffitt, Laura R., Makanji, Ming, Gorrell, Mark D., Oehler, Martin K., Rainczuk, Adam, Stephens, Andrew N., Plebanski, Magdalena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356411/
https://www.ncbi.nlm.nih.gov/pubmed/30602661
http://dx.doi.org/10.3390/cancers11010032
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author Wilson, Amy L.
Wilson, Kirsty L.
Bilandzic, Maree
Moffitt, Laura R.
Makanji, Ming
Gorrell, Mark D.
Oehler, Martin K.
Rainczuk, Adam
Stephens, Andrew N.
Plebanski, Magdalena
author_facet Wilson, Amy L.
Wilson, Kirsty L.
Bilandzic, Maree
Moffitt, Laura R.
Makanji, Ming
Gorrell, Mark D.
Oehler, Martin K.
Rainczuk, Adam
Stephens, Andrew N.
Plebanski, Magdalena
author_sort Wilson, Amy L.
collection PubMed
description 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.
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spelling pubmed-63564112019-02-05 Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model Wilson, Amy L. Wilson, Kirsty L. Bilandzic, Maree Moffitt, Laura R. Makanji, Ming Gorrell, Mark D. Oehler, Martin K. Rainczuk, Adam Stephens, Andrew N. Plebanski, Magdalena Cancers (Basel) Article 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. MDPI 2018-12-31 /pmc/articles/PMC6356411/ /pubmed/30602661 http://dx.doi.org/10.3390/cancers11010032 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wilson, Amy L.
Wilson, Kirsty L.
Bilandzic, Maree
Moffitt, Laura R.
Makanji, Ming
Gorrell, Mark D.
Oehler, Martin K.
Rainczuk, Adam
Stephens, Andrew N.
Plebanski, Magdalena
Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model
title Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model
title_full Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model
title_fullStr Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model
title_full_unstemmed Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model
title_short Non-Invasive Fluorescent Monitoring of Ovarian Cancer in an Immunocompetent Mouse Model
title_sort non-invasive fluorescent monitoring of ovarian cancer in an immunocompetent mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356411/
https://www.ncbi.nlm.nih.gov/pubmed/30602661
http://dx.doi.org/10.3390/cancers11010032
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