Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition

Personalized medicine for breast cancer (BrC) requires predictive biomarkers to select the optimal therapeutic option for each individual patient. Personalization of chemotherapy or immunotherapy responses is particularly challenging, as molecular markers do not appear to be sufficiently predictive...

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Main Authors: Zofia M. Komar, Mieke Bavelaar, Ellen Kageler, Nicole S. Verkaik, Mandy M. van Rosmalen, Carolien H.M. van Deurzen, Michael A. den Bakker, Roland Kanaar, Adriaan B Houtsmuller, Thierry P.P. van den Bosch, Agnes Jager, Dik C. van Gent
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Neoplasia: An International Journal for Oncology Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S1476558625001009
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author Zofia M. Komar
Mieke Bavelaar
Ellen Kageler
Nicole S. Verkaik
Mandy M. van Rosmalen
Carolien H.M. van Deurzen
Michael A. den Bakker
Roland Kanaar
Adriaan B Houtsmuller
Thierry P.P. van den Bosch
Agnes Jager
Dik C. van Gent
author_facet Zofia M. Komar
Mieke Bavelaar
Ellen Kageler
Nicole S. Verkaik
Mandy M. van Rosmalen
Carolien H.M. van Deurzen
Michael A. den Bakker
Roland Kanaar
Adriaan B Houtsmuller
Thierry P.P. van den Bosch
Agnes Jager
Dik C. van Gent
author_sort Zofia M. Komar
collection DOAJ
description Personalized medicine for breast cancer (BrC) requires predictive biomarkers to select the optimal therapeutic option for each individual patient. Personalization of chemotherapy or immunotherapy responses is particularly challenging, as molecular markers do not appear to be sufficiently predictive for therapy response. Functional assays for therapy selection may be the solution for this dilemma. An interesting approach is ex vivo cultures of precision cut tumor slices, such as the MOtion-based Tissue EX vivo (MOTEX) method that we described previously. This culture method has the advantage that it carries all cell types in the tumor, including various immune cell populations. We here show, that macrophages, B-cells and T-cell populations are maintained in the MOTEX culture for several days without apparent loss of viability. Even treatment with the microtubule poison paclitaxel did not reduce immune cell abundance or viability significantly. Anthracycline-based chemotherapy, however, did affect immune cell composition, as expected based on its cytotoxic properties. Therefore, we conclude that MOTEX culture of BrC tissue slices can be used to investigate effect of treatments that involve the immune system. This opens perspectives to develop predictive assays for immune checkpoint inhibitor treatment and other therapeutic interventions that require immune components in the assay system.
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series Neoplasia: An International Journal for Oncology Research
spelling doaj-art-9ef04bc0c7614f5094addf89fc134d222025-08-22T04:55:53ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-10-016810122110.1016/j.neo.2025.101221Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment compositionZofia M. Komar0Mieke Bavelaar1Ellen Kageler2Nicole S. Verkaik3Mandy M. van Rosmalen4Carolien H.M. van Deurzen5Michael A. den Bakker6Roland Kanaar7Adriaan B Houtsmuller8Thierry P.P. van den Bosch9Agnes Jager10Dik C. van Gent11Department of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The NetherlandsDepartment of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The NetherlandsDepartment of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The NetherlandsDepartment of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The NetherlandsDepartment of Pathology, Erasmus MC, Rotterdam, the NetherlandsDepartment of Pathology, Maasstad Ziekenhuis, Rotterdam, the NetherlandsDepartment of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Oncode Institute, Erasmus MC, Rotterdam, The NetherlandsErasmus Optical Imaging Center and Department of Pathology, Erasmus MC, Rotterdam, the NetherlandsDepartment of Pathology, Erasmus MC, Rotterdam, the NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The NetherlandsDepartment of Molecular Genetics, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Oncode Institute, Erasmus MC, Rotterdam, The NetherlandsPersonalized medicine for breast cancer (BrC) requires predictive biomarkers to select the optimal therapeutic option for each individual patient. Personalization of chemotherapy or immunotherapy responses is particularly challenging, as molecular markers do not appear to be sufficiently predictive for therapy response. Functional assays for therapy selection may be the solution for this dilemma. An interesting approach is ex vivo cultures of precision cut tumor slices, such as the MOtion-based Tissue EX vivo (MOTEX) method that we described previously. This culture method has the advantage that it carries all cell types in the tumor, including various immune cell populations. We here show, that macrophages, B-cells and T-cell populations are maintained in the MOTEX culture for several days without apparent loss of viability. Even treatment with the microtubule poison paclitaxel did not reduce immune cell abundance or viability significantly. Anthracycline-based chemotherapy, however, did affect immune cell composition, as expected based on its cytotoxic properties. Therefore, we conclude that MOTEX culture of BrC tissue slices can be used to investigate effect of treatments that involve the immune system. This opens perspectives to develop predictive assays for immune checkpoint inhibitor treatment and other therapeutic interventions that require immune components in the assay system.http://www.sciencedirect.com/science/article/pii/S1476558625001009Tumor microenvironmentBreast cancerTreatment predictionTumor infiltrating lymphocytes (TILs)
spellingShingle Zofia M. Komar
Mieke Bavelaar
Ellen Kageler
Nicole S. Verkaik
Mandy M. van Rosmalen
Carolien H.M. van Deurzen
Michael A. den Bakker
Roland Kanaar
Adriaan B Houtsmuller
Thierry P.P. van den Bosch
Agnes Jager
Dik C. van Gent
Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition
Neoplasia: An International Journal for Oncology Research
Tumor microenvironment
Breast cancer
Treatment prediction
Tumor infiltrating lymphocytes (TILs)
title Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition
title_full Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition
title_fullStr Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition
title_full_unstemmed Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition
title_short Motion based ex vivo (MOTEX) culture of breast tumor slices sustains microenvironment composition
title_sort motion based ex vivo motex culture of breast tumor slices sustains microenvironment composition
topic Tumor microenvironment
Breast cancer
Treatment prediction
Tumor infiltrating lymphocytes (TILs)
url http://www.sciencedirect.com/science/article/pii/S1476558625001009
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