PDX Models: A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast Cancer
The pivotal role of myeloid-derived suppressive cells (MDSCs) in cancer has become increasingly apparent over the past few years. However, to fully understand how MDSCs can promote human tumor progression and to develop strategies to target this cell type, relevant models that closely resemble the c...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/24/6153 |
| _version_ | 1797461065979658240 |
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| author | Morten F. Gjerstorff Sofie Traynor Odd L. Gammelgaard Simone Johansen Christina B. Pedersen Henrik J. Ditzel Mikkel G. Terp |
| author_facet | Morten F. Gjerstorff Sofie Traynor Odd L. Gammelgaard Simone Johansen Christina B. Pedersen Henrik J. Ditzel Mikkel G. Terp |
| author_sort | Morten F. Gjerstorff |
| collection | DOAJ |
| description | The pivotal role of myeloid-derived suppressive cells (MDSCs) in cancer has become increasingly apparent over the past few years. However, to fully understand how MDSCs can promote human tumor progression and to develop strategies to target this cell type, relevant models that closely resemble the clinical complexity of human tumors are needed. Here, we show that mouse MDSCs of both the monocytic (M-MDCS) and the granulocytic (PMN-MDSC) lineages are recruited to human breast cancer patient-derived xenograft (PDX) tumors in mice. Transcriptomic analysis of FACS-sorted MDSC-subpopulations from the PDX tumors demonstrated the expression of several MDSC genes associated with both their mobilization and immunosuppressive function, including <i>S100A8/9</i>, <i>Ptgs2</i>, <i>Stat3</i>, and <i>Cxcr2</i>, confirming the functional identity of these cells. By combining FACS analysis, RNA sequencing, and immune florescence, we show that the extent and type of MDSC infiltration depend on PDX model intrinsic factors such as the expression of chemokines involved in mobilizing and recruiting tumor-promoting MDSCs. Interestingly, MDSCs have been shown to play a prominent role in breast cancer metastasis, and in this context, we demonstrate increased recruitment of MDSCs in spontaneous PDX lung metastases compared to the corresponding primary PDX tumors. We also demonstrate that T cell-induced inflammation enhances the recruitment of MDSC in experimental breast cancer metastases. In conclusion, breast cancer PDX models represent a versatile tool for studying molecular mechanisms that drive myeloid cell recruitment to primary and metastatic tumors and facilitate the development of innovative therapeutic strategies targeting these cells. |
| first_indexed | 2024-03-09T17:14:07Z |
| format | Article |
| id | doaj.art-2f19e5e530e8411cb94f2deb001ca11d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:14:07Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2f19e5e530e8411cb94f2deb001ca11d2023-11-24T13:47:05ZengMDPI AGCancers2072-66942022-12-011424615310.3390/cancers14246153PDX Models: A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast CancerMorten F. Gjerstorff0Sofie Traynor1Odd L. Gammelgaard2Simone Johansen3Christina B. Pedersen4Henrik J. Ditzel5Mikkel G. Terp6Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, J. B. Winsløws Vej 25, 3, DK-5000 Odense, DenmarkDepartment of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, J. B. Winsløws Vej 25, 3, DK-5000 Odense, DenmarkDepartment of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, J. B. Winsløws Vej 25, 3, DK-5000 Odense, DenmarkDepartment of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, J. B. Winsløws Vej 25, 3, DK-5000 Odense, DenmarkDepartment of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, J. B. Winsløws Vej 25, 3, DK-5000 Odense, DenmarkDepartment of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, J. B. Winsløws Vej 25, 3, DK-5000 Odense, DenmarkDepartment of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, J. B. Winsløws Vej 25, 3, DK-5000 Odense, DenmarkThe pivotal role of myeloid-derived suppressive cells (MDSCs) in cancer has become increasingly apparent over the past few years. However, to fully understand how MDSCs can promote human tumor progression and to develop strategies to target this cell type, relevant models that closely resemble the clinical complexity of human tumors are needed. Here, we show that mouse MDSCs of both the monocytic (M-MDCS) and the granulocytic (PMN-MDSC) lineages are recruited to human breast cancer patient-derived xenograft (PDX) tumors in mice. Transcriptomic analysis of FACS-sorted MDSC-subpopulations from the PDX tumors demonstrated the expression of several MDSC genes associated with both their mobilization and immunosuppressive function, including <i>S100A8/9</i>, <i>Ptgs2</i>, <i>Stat3</i>, and <i>Cxcr2</i>, confirming the functional identity of these cells. By combining FACS analysis, RNA sequencing, and immune florescence, we show that the extent and type of MDSC infiltration depend on PDX model intrinsic factors such as the expression of chemokines involved in mobilizing and recruiting tumor-promoting MDSCs. Interestingly, MDSCs have been shown to play a prominent role in breast cancer metastasis, and in this context, we demonstrate increased recruitment of MDSCs in spontaneous PDX lung metastases compared to the corresponding primary PDX tumors. We also demonstrate that T cell-induced inflammation enhances the recruitment of MDSC in experimental breast cancer metastases. In conclusion, breast cancer PDX models represent a versatile tool for studying molecular mechanisms that drive myeloid cell recruitment to primary and metastatic tumors and facilitate the development of innovative therapeutic strategies targeting these cells.https://www.mdpi.com/2072-6694/14/24/6153PDX modelsMDSCbreast cancer |
| spellingShingle | Morten F. Gjerstorff Sofie Traynor Odd L. Gammelgaard Simone Johansen Christina B. Pedersen Henrik J. Ditzel Mikkel G. Terp PDX Models: A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast Cancer Cancers PDX models MDSC breast cancer |
| title | PDX Models: A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast Cancer |
| title_full | PDX Models: A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast Cancer |
| title_fullStr | PDX Models: A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast Cancer |
| title_full_unstemmed | PDX Models: A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast Cancer |
| title_short | PDX Models: A Versatile Tool for Studying the Role of Myeloid-Derived Suppressor Cells in Breast Cancer |
| title_sort | pdx models a versatile tool for studying the role of myeloid derived suppressor cells in breast cancer |
| topic | PDX models MDSC breast cancer |
| url | https://www.mdpi.com/2072-6694/14/24/6153 |
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