Characterization of immune cell populations in syngeneic murine tumor models

Abstract Immunocompetent murine models are important tools for preclinical evaluation of immunotherapies. Here, six different immunocompetent tumor models based on four different cell lines were characterized, including metastatic lung cancer (CMT 167), triple‐negative breast cancer (4T1), pancreati...

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Main Authors: Sofie Snipstad, Frida Bremnes, Mats Dehli Haugum, Einar Sulheim
Format: Article
Language:English
Published: Wiley 2023-05-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.5784
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author Sofie Snipstad
Frida Bremnes
Mats Dehli Haugum
Einar Sulheim
author_facet Sofie Snipstad
Frida Bremnes
Mats Dehli Haugum
Einar Sulheim
author_sort Sofie Snipstad
collection DOAJ
description Abstract Immunocompetent murine models are important tools for preclinical evaluation of immunotherapies. Here, six different immunocompetent tumor models based on four different cell lines were characterized, including metastatic lung cancer (CMT 167), triple‐negative breast cancer (4T1), pancreatic cancer (KPCY), and colon cancer (MC38). The tumors were implanted subcutaneously or orthotopically before the animals were treated with anti‐PD1 checkpoint inhibitor. A range of innate and adaptive immune cells were then quantified by flow cytometry of single‐cell suspensions from the tumors. Furthermore, confocal laser scanning microscopy was used to quantify the density and distribution of T‐cells in frozen sections. A model‐dependent cellular immune landscape was observed, with variable responsiveness toward anti‐PD1, ranging from the most responsive MC38 colon cancer model to the least responsive 4T1 breast cancer model. The study provides an overview of the immune landscape of these tumor models, and a foundation for further elucidation of pro‐tumor and anti‐tumor mechanisms behind heterogeneous responses towards immunotherapies.
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spelling doaj.art-cd74db9f58e54cf69fd13d03e1d5387f2023-06-06T07:30:47ZengWileyCancer Medicine2045-76342023-05-011210115891160110.1002/cam4.5784Characterization of immune cell populations in syngeneic murine tumor modelsSofie Snipstad0Frida Bremnes1Mats Dehli Haugum2Einar Sulheim3Department of Biotechnology and Nanomedicine SINTEF Industry Trondheim NorwayDepartment of Physics Norwegian University of Science and Technology Trondheim NorwayDepartment of Pathology St. Olav's University Hospital Trondheim NorwayDepartment of Biotechnology and Nanomedicine SINTEF Industry Trondheim NorwayAbstract Immunocompetent murine models are important tools for preclinical evaluation of immunotherapies. Here, six different immunocompetent tumor models based on four different cell lines were characterized, including metastatic lung cancer (CMT 167), triple‐negative breast cancer (4T1), pancreatic cancer (KPCY), and colon cancer (MC38). The tumors were implanted subcutaneously or orthotopically before the animals were treated with anti‐PD1 checkpoint inhibitor. A range of innate and adaptive immune cells were then quantified by flow cytometry of single‐cell suspensions from the tumors. Furthermore, confocal laser scanning microscopy was used to quantify the density and distribution of T‐cells in frozen sections. A model‐dependent cellular immune landscape was observed, with variable responsiveness toward anti‐PD1, ranging from the most responsive MC38 colon cancer model to the least responsive 4T1 breast cancer model. The study provides an overview of the immune landscape of these tumor models, and a foundation for further elucidation of pro‐tumor and anti‐tumor mechanisms behind heterogeneous responses towards immunotherapies.https://doi.org/10.1002/cam4.5784animal modelscheckpoint inhibitorimmunotherapytumor immune microenvironment
spellingShingle Sofie Snipstad
Frida Bremnes
Mats Dehli Haugum
Einar Sulheim
Characterization of immune cell populations in syngeneic murine tumor models
Cancer Medicine
animal models
checkpoint inhibitor
immunotherapy
tumor immune microenvironment
title Characterization of immune cell populations in syngeneic murine tumor models
title_full Characterization of immune cell populations in syngeneic murine tumor models
title_fullStr Characterization of immune cell populations in syngeneic murine tumor models
title_full_unstemmed Characterization of immune cell populations in syngeneic murine tumor models
title_short Characterization of immune cell populations in syngeneic murine tumor models
title_sort characterization of immune cell populations in syngeneic murine tumor models
topic animal models
checkpoint inhibitor
immunotherapy
tumor immune microenvironment
url https://doi.org/10.1002/cam4.5784
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AT einarsulheim characterizationofimmunecellpopulationsinsyngeneicmurinetumormodels